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Multiscale 3D Genome Rewiring during Mouse Neural Development
Open accessAbstract
Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We comprehensively mapped 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest-resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating TAD boundaries de novo. Additionally, we discovered long-range contacts between gene bodies of exon-rich, active genes in all cell types. During neural differentiation, contacts between active TADs become less pronounced while inactive TADs interact more strongly. An extensive Polycomb network in stem cells is disrupted, while dynamic interactions between neural transcription factors appear in vivo. Finally, cell type-specific enhancer-promoter contacts are established concomitant to gene expression. This work shows that multiple factors influence the dynamics of chromatin interactions in development.
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TL;DR
Ultra-deep in situ Hi-C across mouse ES cells, neural progenitors, and cortical neurons in vitro and in vivo reveals multiscale 3D genome rewiring during neural differentiation. The study links transcription, CTCF, Polycomb, neural transcription factors, and enhancer-promoter contacts to dynamic chromatin architecture, while showing that transcription alone is not sufficient to create TAD boundaries de novo.
Key findings
- Differentiation involves global compartment reorganization: interactions between active A-type domains decrease, while contacts within inactive B-type domains become stronger; compartment borders decrease with differentiation.
- TADs decrease in number and increase in size; CTCF-less boundaries increase. Developmentally regulated boundaries include 259 ES-specific and 54 neural-specific boundaries. CRISPR-dCas9 activation at Zfp608 and Sox4 caused >10- to 20-fold gene activation but no significant insulation or contact-map change, indicating transcription is correlated with but not sufficient for de novo TAD boundary formation.
- CTCF-mediated loops between convergent CTCF sites increase during differentiation despite decreased CTCF binding; ES-specific CTCF contacts and insulation are lost in NPCs, validated by 3D DNA FISH at the Zfp42 locus.
- Active promoters show CTCF-independent insulation and interact with other active promoters across TAD boundaries; gene bodies of exon-rich, highly expressed genes form long-range contacts in cis and trans, correlating with exon number/splicing. Polycomb-mediated contacts are disrupted during differentiation and correlate with Ring1B rather than H3K27me3. In vivo, neural TFs Pax6, NeuroD2, and Tbr1 organize cell-type-specific contacts, and enhancer-promoter contacts are mostly cell-type specific and generally established concomitantly with gene expression.
Methods
- In situ Hi-C was performed on FACS-purified G0/G1 mouse ES cells, NPCs, and CNs from an in vitro differentiation system, plus NPCs and CNs purified from E14.5 mouse neocortex in vivo. The study reports >40 billion paired-end reads and >17 billion uniquely mapped contacts, with >11 billion uniquely aligned contacts in vitro and ~3 billion per in vivo cell type; maximum resolution reached 750 bp.
- Complementary assays included RNA-seq, ChIP-seq for chromatin marks and factors such as CTCF and Ring1B, 3D DNA FISH, and CRISPR-dCas9-mediated gene activation.
- Hi-C analysis used fragment-end resolution, expected models generated with the Shaman R package, insulation scores, eigenvector-based A/B compartment assignment, aggregate Hi-C maps, and contact enrichment quantification.
Limitations
- The paper states that the in vitro system recapitulates some but not all aspects of cortical development, such as neuronal migration and morphogen signaling; it also notes that whether the observed gene-body contacts are directly linked to co-transcriptional splicing remains to be seen, and whether TF contacts represent true homotypic interactions is unresolved.
- The paper states that clear violations of a simple enhancer-promoter looping model exist, as some enhancer-promoter loops are pre-established.
- Evident from the text: Hi-C is population-averaged and cannot resolve single-cell or allele-specific heterogeneity; FISH validates only selected loci; dCas9 activation was tested at two loci; and in vitro versus in vivo differences may limit generalization.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating TAD boundaries de novo.”
- Also stated in: § Transcription Is Correlated with but Not Sufficient to Induce Insulation at TAD Boundaries De Novo · hedged
“Therefore, transcriptional activation per se appears insufficient to cause chromatin insulation and create a TAD boundary.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Transcription Is Correlated with but Not Sufficient to Induce Insulation at TAD Boundaries De Novo · hedged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An extensive Polycomb network in stem cells is disrupted, while dynamic interactions between neural transcription factors appear in vivo.”
- Also stated in: § Polycomb-Mediated Interactions Are Disrupted Independently of H3K27me3 during Neural Differentiation · boosted
“we observed a strong decrease in contact intensity between common H3K27me3 sites, which was especially notable at long distances (Figure S6A).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Polycomb-Mediated Interactions Are Disrupted Independently of H3K27me3 during Neural Differentiation · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, cell type-specific enhancer-promoter contacts are established concomitant to gene expression.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Additionally, we discovered long-range contacts between gene bodies of exon-rich, active genes in all cell types.”
- Also stated in: § Active Gene Promoters and the Bodies of Exon-Rich Genes Interact at Multiple Genomic Scales · plain
“Finally, actively transcribed genes with a large number of exons engage in long-range chromatin loops in clusters both in cis- and in trans.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Active Gene Promoters and the Bodies of Exon-Rich Genes Interact at Multiple Genomic Scales · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating TAD boundaries de novo.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An extensive Polycomb network in stem cells is disrupted, while dynamic interactions between neural transcription factors appear in vivo.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Abstract
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that genes located in close proximity to the neural-specific TAD boundaries tend to be upregulated (Figures 2Fi and 2Gi)”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Transcription Is Correlated with but Not Sufficient to Induce Insulation at TAD Boundaries De Novo
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: The mechanisms contributing to developmentally regulated TAD borders remain poorly understood.
None of the sources cited for this claim have been checked yet.
In the paper
“we observed a similar increase in insulation around SOX11 (Figure S3M).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Transcription Is Correlated with but Not Sufficient to Induce Insulation at TAD Boundaries De Novo
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The mechanisms contributing to developmentally regulated TAD borders remain poorly understood.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Highly conserved boundaries in our system were characterized by a small but consistent increase in insulation during differentiation (Figures S3D–S3F).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Transcription Is Correlated with but Not Sufficient to Induce Insulation at TAD Boundaries De Novo
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: The mechanisms contributing to developmentally regulated TAD borders remain poorly understood.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Analysis of TAD boundaries revealed that the proportion of the CTCF-less borders increased during differentiation (Figure S3C).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Transcription Is Correlated with but Not Sufficient to Induce Insulation at TAD Boundaries De Novo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 53
- Probably not a substantial claim. 14
- The quote only partly states this claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During neural differentiation, contacts between active TADs become less pronounced while inactive TADs interact more strongly.”
- Also stated in: § Global Reorganization of the 3D Genome during Neural Differentiation · plain
“Surprisingly, the interaction strength between A-type domains decreased, whereas contacts within the B compartment became stronger between NPCs and CNs (Figures 1E and S1L).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Global Reorganization of the 3D Genome during Neural Differentiation · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In total, we sequenced over 40 billion paired-end reads that resulted in more than 17 billion uniquely mapped contacts.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Introduction
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“CTCF was bound to the Sox4 promoter already in ESs, yet insulation dramatically increased only when the gene became expressed at the NPC stage (Figures S3K and S3J).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Transcription Is Correlated with but Not Sufficient to Induce Insulation at TAD Boundaries De Novo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The mechanisms contributing to developmentally regulated TAD borders remain poorly understood.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We then examined TADs and found that their number decreased during differentiation (Figure S3A), with a corresponding increase in size (Figure S3B).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Transcription Is Correlated with but Not Sufficient to Induce Insulation at TAD Boundaries De Novo
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“the correlation between signal enrichment and eigenvector value for active histone marks decreased during differentiation, while the anti-correlation between H3K9me3 and the eigenvector value became stronger”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Global Reorganization of the 3D Genome during Neural Differentiation
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In the paper
“a novel TAD boundary was formed at the transcriptional start site (Tss) of Zfp608 during differentiation (Figure 2H), concomitant with the activation of the gene (Figure S3J) but in the absence of CTCF binding.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Transcription Is Correlated with but Not Sufficient to Induce Insulation at TAD Boundaries De Novo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The mechanisms contributing to developmentally regulated TAD borders remain poorly understood.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed three classes of boundaries: CTCF-positive boundaries, CTCF-negative boundaries close to active gene promoters, and a set of boundaries without enrichment of active marks (Figure 2A).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Transcription Is Correlated with but Not Sufficient to Induce Insulation at TAD Boundaries De Novo
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“cohesin was found both at CTCF-positive boundaries, where it colocalized with CTCF, and on CTCF-negative borders marked by active transcription (Figure 2A).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Transcription Is Correlated with but Not Sufficient to Induce Insulation at TAD Boundaries De Novo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the absolute levels of Ring1B decreased during differentiation (with only a mild effect on gene expression [Figure S6D]), while H3K27me3 levels did not (Figure 5D).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Polycomb-Mediated Interactions Are Disrupted Independently of H3K27me3 during Neural Differentiation
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In the paper
“In contrast, both the contact enrichment and the insulation between ES-specific CTCF regions were decreased in NPCs (Figures 3E, 3F and S4F).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Dynamic CTCF-Based Loops and Insulation during Neural Differentiation
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In the paper
“We observed strong enrichment as expected (Guo et al., 2015, Rao et al., 2014), and the loops were constrained primarily inside TADs and rarely crossed TAD boundaries (Figures 3B and 3D).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Dynamic CTCF-Based Loops and Insulation during Neural Differentiation
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“Conserved CTCF were characterized by strong interactions in the convergent orientation (Figures 3E and 3F) and by strong insulation both in ESs and NPCs (Figure S4E).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Dynamic CTCF-Based Loops and Insulation during Neural Differentiation
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In the paper
“we also identified clusters of very long-range (> 30 Mb) chromatin contacts between bodies of expressed genes in cis (Figures 4I and S5K) and also in trans (Figure S5L).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Active Gene Promoters and the Bodies of Exon-Rich Genes Interact at Multiple Genomic Scales
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In the paper
“most of these interactions were not mediated by CTCF (Figure 4F) and were readily identified in all three cell types (Figure 4G).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Active Gene Promoters and the Bodies of Exon-Rich Genes Interact at Multiple Genomic Scales
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In the paper
“only the 3D FISH distance between the pair of probes containing the forward and the reverse CTCF site increased during differentiation, while the other probe pairs displayed the opposite effect (Figures 3H, S4H, and S4I).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Dynamic CTCF-Based Loops and Insulation during Neural Differentiation
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In the paper
“the contact enrichment between gene bodies was highly correlated not only with expression levels, but also with the number of exons per gene (Figures 4J, 4K, and 4M), and was evident across a large range of genomic distances (Figure S5M) in all three cell types (Figure 4N).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Active Gene Promoters and the Bodies of Exon-Rich Genes Interact at Multiple Genomic Scales
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In the paper
“However, the overall enrichment of CTCF-mediated contacts increased with neural differentiation, and even inter-domain contacts became apparent (Figures 3B–3D and S4B).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Dynamic CTCF-Based Loops and Insulation during Neural Differentiation
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In the paper
“During differentiation, only the forward CTCF site became inaccessible to CTCF, and the chromatin loop disappeared (Figure 3G).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Dynamic CTCF-Based Loops and Insulation during Neural Differentiation
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In the paper
“general TFs such as Taf3 (Liu et al., 2011) appear to enhance interaction between promoters but had little effect on insulation (Figure S5D).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Active Gene Promoters and the Bodies of Exon-Rich Genes Interact at Multiple Genomic Scales
What the sources say
- Not checked yetcites Liu et al., 2011 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“we identified a strong preference for insulation centered on active Tss, but not on inactive ones, a phenomenon that was not dependent on CTCF binding (Figures 4A, 4B, S5A, and S5B).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Active Gene Promoters and the Bodies of Exon-Rich Genes Interact at Multiple Genomic Scales
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In the paper
“We observed that average intra-TAD contacts become stronger, while inter-TAD contacts appear to be depleted during differentiation (Figures 3A and S4A).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Dynamic CTCF-Based Loops and Insulation during Neural Differentiation
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In the paper
“we observed no central enrichment when we performed the same analysis using instead 3′ gene ends (Figure S5F), showing that these interactions were specific to promoters and were correlated with the level of expression (Figures 4H and S5J).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Active Gene Promoters and the Bodies of Exon-Rich Genes Interact at Multiple Genomic Scales
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In the paper
“active chromatin loops span across domains and can be observed even at long distances (Figure 4E), in contrast with CTCF-mediated contacts.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Active Gene Promoters and the Bodies of Exon-Rich Genes Interact at Multiple Genomic Scales
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In the paper
“Therefore, although we confirmed that most TAD boundaries are conserved (Dixon et al., 2012), novel borders can occur at promoters of developmentally regulated genes.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Discussion
What the sources say
- Not checked yetcites Dixon et al., 2012 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Moreover, we identified regions that switch compartments between the in vitro and the in vivo systems, which were accompanied with corresponding changes in gene expression (Figures S8B and S8C).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Cell-Type Specific Chromatin Folding Is Organized around the Neural Transcription Factors Pax6, NeuroD2, and Tbr1 In Vivo
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In the paper
“We observed a strong decrease in the interactions between Sox2 promoter and the ES-specific enhancer (Figure 7G, blue arrow) during differentiation, which coincides with a decrease in both CTCF binding and the H3K27ac mark on the enhancer (Figure 7Gi).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Enhancer-Promoter Contacts Are Mostly Cell-Type Specific and Are Generally Established Concomitantly with Gene Expression
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In the paper
“NeuroD2 and Tbr1 interactions were also mostly constrained inside TADs (Figures 6C, 6D, S7P, and S7Q) but increased during differentiation and were the strongest in CNs in vivo.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Cell-Type Specific Chromatin Folding Is Organized around the Neural Transcription Factors Pax6, NeuroD2, and Tbr1 In Vivo
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In the paper
“These interactions are strongly correlated with the number of splicing events per gene with the strongest contacts occurring between genes that undergo most splicing.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Discussion
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In the paper
“The analysis of a well-controlled differentiation system and its in vivo cell counterparts shows that cell differentiation is accompanied by a global chromatin reorganization and a change in compartmentalization with a decrease in long-range interactions between A-type domains concomitant with an increase in contacts between inactive B-type domains.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Discussion
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In the paper
“In ESs, the strong long-range interactions also involve Polycomb-bound genes and, to a lesser extent, genes bound by pluripotency TFs.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Discussion
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“These networks are reorganized in neuronal differentiation, which in the case of Polycomb appears to correlate with PRC1 binding levels.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Discussion
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In the paper
“We identified a NPC-specific enhancer, which interacted strongly with the promoter of the neuronal TF Brn2 gene only in NPCs, and this interaction was disrupted in CNs when the enhancer was inactive (Figure 7F).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Enhancer-Promoter Contacts Are Mostly Cell-Type Specific and Are Generally Established Concomitantly with Gene Expression
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In the paper
“Principal component analysis (PCA) also confirmed that NPC populations, either in vitro or in vivo, are highly similar to each other and are distinct from CNs and vice versa (Figure S8A).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Cell-Type Specific Chromatin Folding Is Organized around the Neural Transcription Factors Pax6, NeuroD2, and Tbr1 In Vivo
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In the paper
“Furthermore, the average Hi-C scores and the correlation between expression and chromatin contacts were strongly decreased when we randomly shuffled the position of the enhancer region within the same TAD (Figures 7D, 7E, and S8H).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Enhancer-Promoter Contacts Are Mostly Cell-Type Specific and Are Generally Established Concomitantly with Gene Expression
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed a cell-type specific contact enrichment between Pax6-bound sites strongest in ncx NPC where Pax6 is highly expressed (Figures 6C and 6D).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Cell-Type Specific Chromatin Folding Is Organized around the Neural Transcription Factors Pax6, NeuroD2, and Tbr1 In Vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although we did identify instances of pre-set chromatin interactions between enhancers and their cognate target genes that precede transcriptional activation (Figures 7C, S8N, and S8O), the majority of those interactions appear to be established concomitantly to gene expression and are also disrupted when the genes become repressed.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Enhancer-Promoter Contacts Are Mostly Cell-Type Specific and Are Generally Established Concomitantly with Gene Expression
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“mean nuclear radius of the ES, NPC and CNs population were calculated (ES = 1.73 ± 0.28; NPC = 1.39 ± 0.24; CN = 1.43 ± 0.20).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > STAR★Methods > Quantification and Statistical Analysis
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Domains in each cluster exhibit distinct signature based on the enrichment of chromatin marks, replication timing and Lamin B1 DamID enrichment where available (Figure S1I), prompting us to assign cluster 1 to the B-, inactive compartment and cluster 2 to the A-, active compartment.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > STAR★Methods > Quantification and Statistical Analysis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“At intermediate scales (100 kb to 1 Mb), a major discovery is the existence of topologically associating domains (TADs) (Dixon et al., 2012, Nora et al., 2012, Sexton et al., 2012).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Introduction
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We comprehensively mapped 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest-resolution Hi-C maps available to date.”
- Also stated in: § Global Reorganization of the 3D Genome during Neural Differentiation · plain
“We reached a maximum resolution of 750 bp—the highest to date (Figure S1F).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Our understanding of the interaction dynamics at the smallest scales during developmental processes is currently limited.
- Rests on an assumption: The relation between loop extrusion models and transcription remains unclear.
- Also stated in: § Global Reorganization of the 3D Genome during Neural Differentiation · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our data demonstrate that cellular differentiation involves changes at all scales of folding, and in addition to CTCF-dependent processes, it includes major changes in Polycomb and in transcription factor (TF) interaction networks.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Introduction
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Our understanding of the interaction dynamics at the smallest scales during developmental processes is currently limited.
- Rests on an assumption: The relation between loop extrusion models and transcription remains unclear.
In the paper
“At larger scales, interactions between domains are thought to give rise to two main types of spatial compartments referred to as “A” and “B” (Lieberman-Aiden et al., 2009)”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Introduction
What the sources say
- Not checked yetcites Lieberman-Aiden et al., 2009 source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“verified that these borders represent a genuine loss or gain of insulation, respectively, using aggregate Hi-C maps (Figure 2E), insulation score (Figures S3G and S3H), and directionality index (DI) (Figure S3I).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Transcription Is Correlated with but Not Sufficient to Induce Insulation at TAD Boundaries De Novo
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The mechanisms contributing to developmentally regulated TAD borders remain poorly understood.
In the paper
“recent evidence indicates that domains and compartment formation can be at least partially uncoupled and may result from different biological phenomena (Nora et al., 2017).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Introduction
What the sources say
- Not checked yetcites Nora et al., 2017 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Domain insulation has been shown to be important for gene expression and physiology (Flavahan et al., 2016, Lupiáñez et al., 2015).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Introduction
What the sources say
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“which are functionally related to gene expression and can switch extensively during differentiation (Dixon et al., 2015).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Introduction
What the sources say
- Not checked yetcites Dixon et al., 2015 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“very few studies using mostly in vitro cultured cells have achieved high resolution (Rao et al., 2014).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Introduction
What the sources say
- Not checked yetcites Rao et al., 2014 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“we employed a fluorescence-activated cell sorting (FACS) approach, which allowed us to purify G0G1 cells based on DNA content”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Global Reorganization of the 3D Genome during Neural Differentiation
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“we controlled for cell type heterogeneity and cell-cycle variation.”
- Also stated in: § Global Reorganization of the 3D Genome during Neural Differentiation · plain
“we employed a fluorescence-activated cell sorting (FACS) approach, which allowed us to purify G0G1 cells based on DNA content”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Introduction
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Global Reorganization of the 3D Genome during Neural Differentiation · plain
None of the sources cited for this claim have been checked yet.
In the paper
“It is known that architectural proteins such as CTCF and cohesin play a role (Haarhuis et al., 2017, Nora et al., 2017, Phillips-Cremins et al., 2013)”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Introduction
What the sources say
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Biological replicates were highly correlated at all resolutions (Figure S1D) and for each different cell type (Figures S1E and S2A).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Global Reorganization of the 3D Genome during Neural Differentiation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, a major genome-folding reprogramming occurs during neural differentiation with a progressive increase in compartment size, decreased interactions within the A compartment, and a concomitant increase in interactions between B-type domains.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Global Reorganization of the 3D Genome during Neural Differentiation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Our understanding of the interaction dynamics at the smallest scales during developmental processes is currently limited.
- Rests on an assumption: The relation between loop extrusion models and transcription remains unclear.
None of the sources cited for this claim have been checked yet.
In the paper
“The deposition of chromatin marks is thought to contribute to this process (Dixon et al., 2015, Nora et al., 2012)”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Introduction
What the sources say
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, promoters of active genes are characterized by strong insulation, which is correlated with transcriptional activity, but is mostly CTCF independent.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Active Gene Promoters and the Bodies of Exon-Rich Genes Interact at Multiple Genomic Scales
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Polycomb-mediated interactions have been previously reported in mouse ESs using a Capture-C approach (Schoenfelder et al., 2015b) and are a prominent feature in Drosophila (Bantignies et al., 2011).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Polycomb-Mediated Interactions Are Disrupted Independently of H3K27me3 during Neural Differentiation
What the sources say
- Not checked yetcites Schoenfelder et al., 2015b
- Not checked yetcites Bantignies et al., 2011 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Active Tss maintain contacts with the gene body and, contrary to CTCF interactions, can interact with other transcribed Tss across TAD boundaries.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Active Gene Promoters and the Bodies of Exon-Rich Genes Interact at Multiple Genomic Scales
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“As many as 40–50% of the CTCF sites may change in different cell types (Chen et al., 2012).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Dynamic CTCF-Based Loops and Insulation during Neural Differentiation
What the sources say
- Not checked yetcites Chen et al., 2012 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Chromatin insulation occurs at multiple levels and leads to a hierarchical 3D nuclear organization, whereby smaller, less insulated regions (called also sub-TADs [Flavahan et al., 2016, Phillips-Cremins et al., 2013] or contact domains [Rao et al., 2014]) are nested inside TADs, which are usually bigger and more strongly insulated (Dixon et al., 2012, Nora et al., 2012, Sexton et al., 2012).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Dynamic CTCF-Based Loops and Insulation during Neural Differentiation
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, very few public chromatin immunoprecipitation sequencing (ChIP-seq) profiles exist, and most of those have been performed in the developing mouse neocortex (Bayam et al., 2015, Notwell et al., 2016, Sun et al., 2015).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Cell-Type Specific Chromatin Folding Is Organized around the Neural Transcription Factors Pax6, NeuroD2, and Tbr1 In Vivo
What the sources say
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We performed RNA-seq and verified our approach using known markers for neural progenitors (Nestin) and differentiating neurons (Dcx) (Figure S7D).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Cell-Type Specific Chromatin Folding Is Organized around the Neural Transcription Factors Pax6, NeuroD2, and Tbr1 In Vivo
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Pearson correlation coefficient (Figure S7E), comparison of the eigenvector values, insulation score, and contact probability (Figures S7G and S8A) confirmed the high quality of the data and that, importantly, samples group together based on cell type.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Cell-Type Specific Chromatin Folding Is Organized around the Neural Transcription Factors Pax6, NeuroD2, and Tbr1 In Vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Pax6 is one of the few “master regulator” neural TFs with a well-known role in cortical development (Manuel et al., 2015).”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Cell-Type Specific Chromatin Folding Is Organized around the Neural Transcription Factors Pax6, NeuroD2, and Tbr1 In Vivo
What the sources say
- Not checked yetcites Manuel et al., 2015 source
Strength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that E-P interactions are highly dynamic and cell-type specific.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Results > Enhancer-Promoter Contacts Are Mostly Cell-Type Specific and Are Generally Established Concomitantly with Gene Expression
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, E-P interactions are highly dynamic and are usually established concomitantly with gene expression.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Boundaries within 10Kb of each other were merged and only boundaries, which were detected in at least 3 biological replicates, were retained.”
§ Multiscale 3D Genome Rewiring during Mouse Neural Development > STAR★Methods > Quantification and Statistical Analysis
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
The paper relies on this without support.
Our understanding of the interaction dynamics at the smallest scales during developmental processes is currently limited.
“However, our understanding of the interaction dynamics at the smallest scales during developmental processes is currently limited.”
The paper relies on this without support.
The relation between loop extrusion models and transcription remains unclear.
“However, the relation between such models and transcription remains unclear.”
The paper relies on this without support.
The mechanisms contributing to developmentally regulated TAD borders remain poorly understood.
“yet the mechanisms contributing to developmentally regulated borders remain poorly understood.”
The paper relies on this without support.
The majority of strong Polycomb-bound regions are on gene promoters.
“As the majority of strong Polycomb-bound regions are on gene promoters, we examined whether their interaction might depend on paused Pol II that is located at bivalent gene promoters (Min et al., 2011).”
The paper relies on this without support.
Enhancer-promoter contacts have been difficult to observe in Hi-C, and their strength relative to surrounding regions is unclear.
“Enhancer-promoter (E-P) contacts have been difficult to observe in Hi-C, and it is unclear how strong they are compared to the surrounding regions.”
The paper relies on this without support.
The in vitro differentiation system recapitulates some aspects of cortical development but not others such as neuronal migration and morphogen signaling.
“Furthermore, although the in vitro system we employed recapitulates some aspects of cortical development, other features, such as neuronal migration and morphogen signaling, are not.”
The paper relies on this without support.
The vast majority of ultra-close cis Hi-C contacts (separated by less than 1 kb) originate from non-digested DNA.
“Contacts separated by less than 1kb were not considered for subsequent analysis, as the vast majority of this ultra-close cis contacts originate from non-digested DNA.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The Sox2 gene has an essential enhancer, the Sox2 Control Region (SCR), which was found by 3C-derived techniques to loop to the Sox2 promoter (for example, [379, 401]).”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [401]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“active promoters and enhancers can likely give rise to TAD boundaries even in the absence of convergent CTCF sites [401].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [401]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Interestingly, Hi-C data obtained using differentiated mouse neurons led us to detect chromatin interactions between HAR202 and the Npas3 promoter (Bonev et al. 2017; supplementary fig. S8, Supplementary Material online).”
From The Human Accelerated Region HAR202 Controls NPAS3 Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences (2024) · cites this paper as Bonev et al. 2017
The cited source says what the claim attributes to it.
In the citing paper
“The majority of specific enhancer–promoter loops follow this pattern and are highly enriched within, compared with across, TAD boundaries [277, 401, 405].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [401]
In the citing paper
“The 3D genome plays an important role in neuronal gene expression and function”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [96]
In the citing paper
“5C maps from our mature primary cortical neurons were highly correlated with and exhibited similar loops as published Hi-C maps from ES cell-derived cortical neurons”
From Three-dimensional genome restructuring across timescales of activity-induced neuronal gene expression (2020) · cites this paper as [33]
In the citing paper
“We applied published methods17 to identify 24,937 loops in cortical neurons”
From Three-dimensional genome restructuring across timescales of activity-induced neuronal gene expression (2020) · cites this paper as [33]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Guide RNA is labeled for a different gene than the reported activation target
MinorThe experiment is described as activating Zfp608 and Sox4, but the methods label one of the guide RNAs "Zfp604." As written, the stated guide target does not match the gene used for the reported Zfp608 activation result.
“We used the CRISPR-dCas9 system (Konermann et al., 2015) to activate gene expression at the endogenous Zfp608 and Sox4 loci”
“Guide RNAs (Zfp604 – AGAAAGCGGAATGAGAAGTT and Sox4 - TTGCTCTGTAAATTGGAATG) were designed and cloned”
Deposited-data table labels the CN RNA sample as NPC
MinorThe table lists both complementary sorted populations as ncx_NPC, whereas the paper identifies Hes5-GFP−/Dcx-mRFP+ cells as ncx CN.
“| Strand specific total RNA from sorted Hes5-GFP-/Dcx-mRFP+ ncx_NPC cells | This study | GEO: GSE96107 |”
“GFP-/RFP+ (“ncx CN”) populations from the same embryonic brains”
In vivo sorting methods list the NPC population twice
MinorThe figure identifies GFP+/RFP− cells as NPCs and GFP−/RFP+ cells as CNs. The isolation methods instead list GFP+/RFP− and RFP−/GFP+-the same population in reversed notation-rather than the CN population.
“The appropriate gates to isolate GFP+/RFP- and RFP-/GFP+ cells were set as described in Figure S7B.”
“GFP+/RFP- (referred to as “ncx NPC” henceafter) and GFP-/RFP+ (“ncx CN”) populations from the same embryonic brains”
Cacna2d1 contact distance exceeds the stated map region
MinorThe text places the interacting Ring1B site approximately 500 kb downstream of the Cacna2d1 promoter, but the Figure S6J caption says its map shows an approximately 150-kb region around that promoter containing the interaction. A 150-kb region cannot contain both sites as described.
“a loop was formed specifically in NPCs between the Cacna2d1 promoter and another NPC-specific Ring1B site located ∼500 kb downstream in the gene body (Figure S6J).”
“(J) HiC contact maps showing ∼150Kb region around Cacna2d1 promoter. Note the appearance of NPC-specific Ring1B/H3K27me3 site inside Cacna2d1 gene body, which coincides with an interaction between this region and the Cacna2d1 promoter.”
Citations
Cites
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Rao, S. S. P., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., Robinson, J. T., Sanborn, A. L., Machol, I., Omer, A. D., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.021 · Cited by 9,212
Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
Lieberman-Aiden, E., van Berkum, N. L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B. R., Sabo, P. J., Dorschner, M. O., et al. (2009) · Science · doi:10.1126/science.1181369 · Cited by 8,898
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J. S., & Ren, B. (2012) · Nature · doi:10.1038/nature11082 · Cited by 6,829
Spatial partitioning of the regulatory landscape of the X-inactivation centre
Nora, E. P., Lajoie, B. R., Schulz, E. G., Giorgetti, L., Okamoto, I., Servant, N., Piolot, T., van Berkum, N. L., Meisig, J., Sedat, J., et al. (2012) · Nature · doi:10.1038/nature11049 · Cited by 2,895
Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex
Konermann, S., Brigham, M. D., Trevino, A. E., Joung, J., Abudayyeh, O. O., Barcena, C., Hsu, P. D., Habib, N., Gootenberg, J. S., Nishimasu, H., et al. (2015) · Nature · doi:10.1038/nature14136 · Cited by 2,825
Disruptions of Topological Chromatin Domains Cause Pathogenic Rewiring of Gene-Enhancer Interactions
Lupiáñez, D. G., Kraft, K., Heinrich, V., Krawitz, P., Brancati, F., Klopocki, E., Horn, D., Kayserili, H., Opitz, J. M., Laxova, R., et al. (2015) · Cell · doi:10.1016/j.cell.2015.04.004 · Cited by 2,132
Formation of chromosomal domains by loop extrusion
Fudenberg, G., Imakaev, M., Lu, C., Goloborodko, A., Abdennur, N., & Mirny, L. A. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.085 · Cited by 2,003
Three-dimensional folding and functional organization principles of the Drosophila genome
Sexton, T., Yaffe, E., Kenigsberg, E., Bantignies, F., Leblanc, B., Hoichman, M., Parrinello, H., Tanay, A., & Cavalli, G. (2012) · Cell · doi:10.1016/j.cell.2012.01.010 · Cited by 1,983
Self-citationMediator and cohesin connect gene expression and chromatin architecture
Kagey, M. H., Newman, J. J., Bilodeau, S., Zhan, Y., Orlando, D. A., van Berkum, N. L., Ebmeier, C. C., Goossens, J., Rahl, P. B., Levine, S. S., et al. (2010) · Nature · doi:10.1038/nature09380 · Cited by 1,939
Sanborn, A. L., Rao, S. S. P., Huang, S.-C., Durand, N. C., Huntley, M. H., Jewett, A. I., Bochkov, I. D., Chinnappan, D., Cutkosky, A., Li, J., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1518552112 · Cited by 1,730
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Modeling epigenetic lesions that cause gliomas
Rahme, G. J., Javed, N. M., Puorro, K. L., Xin, S., Hovestadt, V., Johnstone, S. E., & Bernstein, B. (2023) · Cell · doi:10.1016/j.cell.2023.06.022 · Cited by 75
Patrick, R., Naval-Sánchez, M., Deshpande, N., Huang, Y., Zhang, J., Chen, X., Yang, Y., Tiwari, K., Esmaeili, M., Tran, M., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.06.006 · Cited by 76
Order and disorder: abnormal 3D chromatin organization in human disease
Anania, C., & Lupiáñez, D. G. (2019) · Briefings in Functional Genomics · doi:10.1093/bfgp/elz028 · Cited by 74
“In contrast, CTCF-independent loops are more dynamic and associated to interactions that relate directly to the transcriptional process, such as enhancer-promoter or Polycomb-mediated contacts [10, 12].”
BackgroundAnopheles mosquitoes reveal new principles of 3D genome organization in insects
Lukyanchikova, V., Nuriddinov, M., Belokopytova, P. S., Taskina, A., Liang, J., Reijnders, M. J. M. F., Ruzzante, L., Feron, R., Waterhouse, R. M., Wu, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29599-5 · Cited by 76
Transposable elements drive reorganisation of 3D chromatin during early embryogenesisPreprint
Kruse, K., Díaz, N., Enriquez-Gasca, R., Gaume, X., Torres‐Padilla, M., & Vaquerizas, J. M. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/523712 · Cited by 79
“…previous observations during ZGA in Drosophila (Hug et al. 2017) and echoing recent observations of TAD boundary formation during cortical neuron development (Bonev et al. 2017), the establishment of TAD boundaries coincides with the recruitment of RNA Pol II and active transcription at those loci.”
BackgroundInfluentialQuantitative prediction of enhancer–promoter interactionsPreprint
Belokopytova, P. S., Mozheiko, E. A., Nuriddinov, M. A., Fishman, D., & Fishman, V. (2019) · Genome Research · doi:10.1101/gr.249367.119 · Cited by 71
Brown, J. M., Roberts, N. A., Graham, B., Waithe, D., Lagerholm, C., Telenius, J. M., De Ornellas, S., Oudelaar, A. M., Scott, C., Szczerbal, I., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06248-4 · Cited by 72
Santos, M. D., Backer, S., Aurade, F., Wong, M. M.-K., Wurmser, M., Pierre, R., Vives, F. L., Cruzeiro, M. D., Schmitt, A., Concordet, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28666-1 · Cited by 75
From 1D sequence to 3D chromatin dynamics and cellular functions: a phase separation perspective
Liu, S., Zhang, L., Quan, H., Tian, H., Meng, L., Yang, L., Feng, H., & Gao, Y. Q. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky633 · Cited by 66
“Whereas differentiation and senescence are associated with the non-specific segregation of forests and prairies into different compartments, as well as the establishment of TF-mediated specific genomic interactions (57,66,75,81,82).”
BackgroundGirdhar, K., Hoffman, G. E., Bendl, J. M., Rahman, S., Dong, P., Liao, W., Hauberg, M. E., Sloofman, L. G., Brown, L. M., Devillers, O., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01032-6 · Cited by 64
Matthews, B. J., & Waxman, D. J. (2018) · eLife · doi:10.7554/elife.34077 · Cited by 66
“All Hi-C 978 datasets used were publicly available for mouse [15, 51] and human cells [15] (Supplementary File 4).”
BackgroundMethodInfluentialApproaches and advances in the genetic causes of autoimmune disease and their implications
Inshaw, J. R. J., Cutler, A. J., Burren, O. S., Stefana, M. I., & Todd, J. A. (2018) · Nature Immunology · doi:10.1038/s41590-018-0129-8 · Cited by 70
Transcription factors: building hubs in the 3D space
Giammartino, D. C. D., Polyzos, A., & Apostolou, E. (2020) · Cell Cycle · doi:10.1080/15384101.2020.1805238 · Cited by 67
“The development of Hi-C technology which allows genomewide mapping of regions in physical proximity further improved our understanding of the organizational principles of 3D chromatin topology and the association with gene expression [30,31].”
BackgroundApplications of deep learning in understanding gene regulation
Li, Z., Gao, E., Zhou, J., Han, W., Xu, X., & Gao, X. (2023) · Cell Reports Methods · doi:10.1016/j.crmeth.2022.100384 · Cited by 72
Self-citationSignaling by Steroid Hormones in the 3D Nuclear Space
Dily, F. L., & Beato, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020306 · Cited by 76
“Through the process of differentiation, chromosomal domains can dynamically switch from one to the other compartment, in correlation with changes of expression of tissue specific genes [23,39].”
BackgroundGene regulation in the 3D genome
Li, Y., Hu, M., & Shen, Y. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy164 · Cited by 71
“Dynamic and cell type-specific chromatin loops between enhancers and promoter usually occur within TAD (7,58) and mediated by CTCF, cohesion complex and mediator complex (18,59).”
BackgroundPCGF5 is required for neural differentiation of embryonic stem cells
Yao, M., Zhou, X., Zhou, J., Gong, S., Hu, G., Li, J., Huang, K., Lai, P., Shi, G. W., Hutchins, A. P., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03781-0 · Cited by 66
Mesoscale modeling reveals formation of an epigenetically driven HOXC gene hub
Bascom, G. D., Myers, C. G., & Tamar Schlick, A. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1816424116 · Cited by 69
“Changes in epigenetic features are part of the regulation of development (31), differentiation (32), and cancer progression (33).”
BackgroundPacheco-Bernal, I., Becerril-Pérez, F., & Aguilar‐Arnal, L. (2019) · Clinical Epigenetics · doi:10.1186/s13148-019-0677-2 · Cited by 67
“example, cell-type-specific contacts between loci bound by distinct transcription factors are apparent during neural differentiation [77].”
BackgroundThe regulatory landscapes of developmental genes
Bolt, C. C., & Duboule, D. (2020) · Development · doi:10.1242/dev.171736 · Cited by 66
“TADs are relatively small genomic regions (approximately 1 Mb on average) (Bonev et al., 2017), and appear to be produced in part by the zinc-finger protein CTCF and the cohesin complex.”
BackgroundThe interdependence of gene-regulatory elements and the 3D genome
Vermunt, M. W., Zhang, D., & Blobel, G. A. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201809040 · Cited by 72
“Uniformity of TADs across tissues also suggests that gene expression cannot be the only determinant of TAD formation even though it likely contributes to it (Bonev et al., 2017).”
BackgroundHan, X., Zhang, J., Liu, Y., Fan, X., Ai, S., Luo, Y., Li, X., Jin, H., Luo, S., Zheng, H., et al. (2019) · Development · doi:10.1242/dev.176198 · Cited by 69
Chromatin-mediated alternative splicing regulates cocaine-reward behavior
Xu, S.-J., Lombroso, S. I., Fischer, D. K., Carpenter, M. D., Marchione, D. M., Hamilton, P. J., Lim, C. J., Neve, R. L., Garcia, B. A., Wimmer, M. E., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.08.008 · Cited by 63
Cresswell, K. G., Stansfield, J. C., & Dozmorov, M. G. (2020) · BMC Bioinformatics · doi:10.1186/s12859-020-03652-w · Cited by 64
Interpreting the impact of noncoding structural variation in neurodevelopmental disorders
D’haene, E., & Vergult, S. (2020) · Genetics in Medicine · doi:10.1038/s41436-020-00974-1 · Cited by 63
Xist RNA antagonizes the SWI/SNF chromatin remodeler BRG1 on the inactive X chromosome
Jégu, T., Blum, R., Cochrane, J. C., Yang, L., Wang, C., Gilles, M.-E., Colognori, D., Szántó, A., Marr, S. K., Kingston, R. E., et al. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0176-8 · Cited by 64
“Formation of superloops is in line with the idea of self-association of chromatin with the same properties 5,49–51 , 58 .”
HOX gene cluster (de)regulation in brain: from neurodevelopment to malignant glial tumours
Gonçalves, C. S., Boiteux, E. L., Arnaúd, P., & Costa, B. M. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03508-9 · Cited by 63
Cohesin: behind dynamic genome topology and gene expression reprogramming
Perea-Resa, C., Wattendorf, L., Marzouk, S., & Blower, M. D. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.03.005 · Cited by 63
Vos, E. S. M., Valdes‐Quezada, C., Huang, Y., Allahyar, A., Verstegen, M. J. A. M., Felder, A.-K., van der Vegt, F., Uijttewaal, E. C. H., Krijger, P. H. L., & de Laat, W. L. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.06.008 · Cited by 61
Chang, L., Ghosh, S., Papale, A., Luppino, J. M., Miranda, M., Piras, V., Degrouard, J., Edouard, J., Poncelet, M., Lecouvreur, N., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41265-y · Cited by 63
Hung, T.-C., Kingsley, D. M., & Boettiger, A. N. (2024) · Nature Genetics · doi:10.1038/s41588-023-01641-2 · Cited by 64
Cell Fate and Developmental Regulation Dynamics by Polycomb Proteins and 3D Genome Architecture
Loubière, V., Martinez, A., & Cavalli, G. (2019) · BioEssays · doi:10.1002/bies.201800222 · Cited by 63
Self-citationEssential role of Cp190 in physical and regulatory boundary formation
Kaushal, A., Dorier, J., Wang, B., Mohana, G., Taschner, M., Cousin, P., Waridel, P., Iseli, C., Semenova, A., Restrepo, S., et al. (2022) · Science Advances · doi:10.1126/sciadv.abl8834 · Cited by 64
“Recombinant protein pull-downs Expression plasmids encoding untagged full-length Cp190[1-1096] and/or Cp60[1-440] (with kanamycin resistance) were cotransformed with a plasmid expressing GFP-tagged CTCF[1-293] (N terminus), CTCF[610-818] (C terminus), Su(Hw)[1-219] (N terminus), Su(Hw)[724-941] (C terminus), Ibf1[1-24…”
BackgroundMethodInfluentialCTCF organizes inter-A compartment interactions through RYBP-dependent phase separation
Wei, C., Jia, L., Huang, X., Tan, J., Wang, M., Niu, J., Hou, Y., Sun, J.-Y., Zeng, P., Wang, J., et al. (2022) · Cell Research · doi:10.1038/s41422-022-00676-0 · Cited by 55
“Cell differentiation is accompanied by global reorganization of chromatin structures and changes in long-range chromatin interactions between compartments.(13) The extremely long-range promoter–promoter interactions are established during the ground-state to primed-state pluripotency transition.”
BackgroundNa, J., Tai, C., Wang, Z., Yang, Z., Chen, X., Zhang, J., Zheng, L., & Fan, Y. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122715 · Cited by 66
Active Fluctuations of the Nuclear Envelope Shape the Transcriptional Dynamics in Oocytes
Almonacid, M., Jord, A. A., El‐Hayek, S., Othmani, A., Coulpier, F., Lemoine, S., Miyamoto, K., Grosse, R., Klein, C., Piolot, T., et al. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.09.010 · Cited by 63
Spatial Organization of Chromatin: Emergence of Chromatin Structure During Development
Ghosh, R. P., & Meyer, B. J. (2021) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-032321-035734 · Cited by 60
“Using ultra-deep Hi-C analysis of genome-wide chromosome contacts in models of neural differentiation and cortical development, Bonev et al. (2017) showed that neural differentiation involves changes in genome folding over multiple scales that occur through a variety of mechanisms.”
BackgroundAmin, R., Shukla, A., Zhu, J. J., Kim, S., Wang, P., Tian, S. Z., Tran, A. D., Paul, D., Cappell, S. D., Burkett, S. S., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27451-w · Cited by 62
Clarkson, C. T., Deeks, E. A., Samarista, R., Mamayusupova, H., Zhurkin, V. B., & Teif, V. B. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz908 · Cited by 63
“Next we compared nucleosome positioning around CTCF motifs upon differentiation of ESCs to neural progenitor cells (NPSs) and mouse embryonic fibroblasts (MEFs) using MNase-seq data from (36) and CTCF ChIP-seq data from (9,42) (Figure 7A).”
InfluentialHiC-DC+ enables systematic 3D interaction calls and differential analysis for Hi-C and HiChIP
Sahin, M., Wong, W., Zhan, Y.-Q. A., Deynze, K. V., Koche, R., & Leslie, C. (2021) · Nature Communications · doi:10.1038/s41467-021-23749-x · Cited by 57
Higher-Order Chromosomal Structures Mediate Genome Function
Jerković, I., Szabo, Q., Bantignies, F., & Cavalli, G. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.10.014 · Cited by 57
Self-citationDefining Functionally Relevant Spatial Chromatin Domains: It is a TAD Complicated
Sikorska, N., & Sexton, T. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.006 · Cited by 65
Stefano, M. D., Stadhouders, R., Farabella, I., Castillo, D., Serra, F., Graf, T., & Martí-Renom, M. A. (2020) · Nature Communications · doi:10.1038/s41467-020-16396-1 · Cited by 63
“The models, however, suggest a common mechanism for all the 21 loci upon activation that promoter-enhancer communication 52 occurs via direct interactions between distant enhancers and its cognate target gene as previously observed in many studies 33,46,49,50,53 – 62 .”
BackgroundMethodZhu, Y., Yu, J., Gu, J., Xue, C., Zhang, L., Chen, J., & Shen, L. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1069 · Cited by 59
“Thus, our results support previous observations that transcription is not sufficient to cause chromatin insulation (30).”
Enhancer-gene specificity in development and disease
Pachano, T., Haro, E., & Rada-Iglesias, Á. (2022) · Development · doi:10.1242/dev.186536 · Cited by 57
Gupta, S., & Santoro, R. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.08.012 · Cited by 65
Transcriptional networks controlling stromal cell differentiation
Rauch, A., & Mandrup, S. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00357-7 · Cited by 57
Chromatin Conformation in Development and Disease
Boltsis, I., Grosveld, F. G., Giraud, G., & Kolovos, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.723859 · Cited by 59
“When these enhancers are activated during differentiation of ESCs to neural progenitors, the interaction with their cognate genes is preserved, leading to their activation (Cruz-Molina et al., 2017).”
BackgroundResultInfluentialLin, D., Xu, W., Hong, P., Wu, C., Zhang, Z., Zhang, S., Xing, L., Yang, B., Zhou, W., Xiao, Q., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33558-5 · Cited by 61
Reorganized 3D Genome Structures Support Transcriptional Regulation in Mouse Spermatogenesis
Luo, Z., Wang, X., Jiang, H., Wang, R., Chen, J., Chen, Y., Xu, Q., Cao, J., Gong, X., Wu, J., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101034 · Cited by 56
Schoenfelder, S., Mifsud, B., Senner, C. E., Todd, C. D., Chrysanthou, S., Darbo, E., Hemberger, M., & Branco, M. R. (2018) · Nature Communications · doi:10.1038/s41467-018-06666-4 · Cited by 54
Topologically Associating Domains and Regulatory Landscapes in Development, Evolution and Disease
Tena, J. J., & Santos-Pereira, J. M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.702787 · Cited by 65
“Indeed, enhancer-promoter interactions are highly dynamic and cell-type-specific during neural and erythroid differentiation, accompanying the activation of lineagespecific genes (Bonev et al., 2017; Oudelaar et al., 2020; Kubo et al., 2021).”
BackgroundReed, K. S. M., Davis, E. S., Bond, M. L., Cabrera, A., Thulson, E., Quiroga, I. Y., Cassel, S., Woolery, K. T., Hilton, I. B., Won, H., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111567 · Cited by 56
“3C-based time courses of biological transitions have produced valuable insights into the dynamics of 3D chromatin architecture (Bonev et al., 2017; Abramo et al., 2019; Bertero et al., 2019; Zhang et al., 2019a, 2019b; Yang et al., 2020; Furlan-Magaril et al., 2021; Vilarrasa-Blasi et al., 2021).”
BackgroundBauer, M., Vidal, E., Zorita, E. V., Üresin, N., Pinter, S. F., Filion, G. J. P., & Payer, B. (2021) · Nature Communications · doi:10.1038/s41467-021-23610-1 · Cited by 54
The chromatin remodeling enzyme Chd4 regulates genome architecture in the mouse brain
Goodman, J. V., Yamada, T., Yang, Y., Kong, L., Wu, D. Y., Zhao, G., Gabel, H. W., & Bonni, A. (2020) · Nature Communications · doi:10.1038/s41467-020-17065-z · Cited by 57
Chromatin architecture reorganization during neuronal cell differentiation in Drosophila genomePreprint
Chathoth, K. T., & Zabet, N. R. (2019) · Genome Research · doi:10.1101/gr.246710.118 · Cited by 56
Taylor, T., Sikorska, N., Shchuka, V. M., Chahar, S., Ji, C., Macpherson, N. N., Moorthy, S. D., de Kort, M. A. C., Mullany, S., Khader, N., et al. (2022) · Genes & Development · doi:10.1101/gad.349489.122 · Cited by 45
“Previous studies have shown that abolition of the Sox2 – SCR TAD upon ESC differentiation to neuronal pre-cursors (Bonev et al. 2017) was associated with a complete loss of promoter – enhancer interactions within only a few days of in vitro differentiation (Ben Zouari et al. 2020).”
InfluentialZNF143 is a regulator of chromatin loop
Wen, Z., Huang, Z.-T., Zhang, R., & Peng, C. (2018) · Cell Biology and Toxicology · doi:10.1007/s10565-018-9443-z · Cited by 41
“The similar relationship between chromatin loop and gene expression was observed in the neuron cell differentiation (Bonev et al. 2017).”
BackgroundMultiplex-GAM: genome-wide identification of chromatin contacts yields insights overlooked by Hi-C
Beagrie, R. A., Thieme, C. J., Annunziatella, C., Baugher, C., Zhang, Y., Schueler, M., Kukalev, A., Kempfer, R., Chiariello, A. M., Bianco, S., et al. (2023) · Nature Methods · doi:10.1038/s41592-023-01903-1 · Cited by 61
ATP, Mg2+, Nuclear Phase Separation, and Genome Accessibility
Wright, R. H. G., Dily, F. L., & Beato, M. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2019.03.001 · Cited by 54
Amat, R., Böttcher, R., Dily, F. L., Vidal, E., Quilez, J., Cuartero, Y., Beato, M., de Nadal, E., & Posas, F. (2018) · Genome Research · doi:10.1101/gr.238527.118 · Cited by 58
Three-dimensional organization and dynamics of the genome
Szałaj, P., & Plewczyński, D. (2018) · Cell Biology and Toxicology · doi:10.1007/s10565-018-9428-y · Cited by 59
“Interestingly, it was found that these contacts are strongly correlated with the number of gene exons, suggesting that they may be involved in splicing (Bonev et al. 2017)).”
BackgroundInfluentialGene regulatory mechanisms underlying sex differences in brain development and psychiatric disease
Manoli, D. S., & Tollkühn, J. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13564 · Cited by 58
Yang, L., Chen, F., Zhu, H.-C., Chen, Y., Dong, B., Shi, M.-L., Wang, W., Jiang, Q., Zhang, L.-P., Huang, X., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24044-5 · Cited by 44
Song, Y., Liang, Z., Zhang, J., Hu, G.-C., Wang, J.-H., Li, Y.-Y., Guo, R., Dong, X.-T., Babarinde, I. A., Ping, W., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110626 · Cited by 46
Challenges and guidelines toward 4D nucleome data and model standards
Martí-Renom, M. A., Almouzni, G., Bickmore, W. A., Bystricky, K., Cavalli, G., Fraser, P., Gasser, S. M., Giorgetti, L., Heard, É., Nicodemi, M., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0236-3 · Cited by 53
“The analysis of carefully controlled cell differentiation systems should be complemented by in vivo work from sorted cells 103 , and particularly in the case of humans, a valuable alternative is the use of organoids obtained from differentiation of ES or iPS cells.”
Self-citationMultiscale 3D genome reorganization during skeletal muscle stem cell lineage progression and aging
Zhao, Y. F., Ding, Y., He, L., Zhou, Q., Chen, X., Li, Y., Alfonsi, M. V., Wu, Z., Sun, H., & Wang, H. (2023) · Science Advances · doi:10.1126/sciadv.abo1360 · Cited by 56
Regulation of Chromatin Structure During Neural Development
Kishi, Y., & Gotoh, Y. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00874 · Cited by 51
Selfish: discovery of differential chromatin interactions via a self-similarity measure
Ardakany, A. R., Ay, F., & Lonardi, S. (2019) · Bioinformatics · doi:10.1093/bioinformatics/btz362 · Cited by 52
“In our final experiment to assess the performance of two methods, we tested Selfish and FIND on a real test case from Bonev et al. (2017). Figure 8 shows a 2-Mb region around the Brn2 promoter (also known as Pou3f2) for mouse embryonic stem cells (ES) and neuronal progenitor cells (NPC).”
MethodThe stochastic nature of genome organization and function
Sood, V., & Misteli, T. (2021) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2021.10.004 · Cited by 53
Chromatin Remodelers in the 3D Nuclear Compartment
Magaña‐Acosta, M., & Valadéz-Graham, V. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.600615 · Cited by 58
Chovanec, P., Collier, A. J., Krueger, C., Várnai, C., Semprich, C. I., Schoenfelder, S., Corcoran, A. E., & Rugg‐Gunn, P. J. (2021) · Nature Communications · doi:10.1038/s41467-021-22201-4 · Cited by 48
Raviram, R., Rocha, P. P., Luo, V. M., Swanzey, E., Miraldi, E. R., Chuong, E. B., Feschotte, C., Bonneau, R., & Skok, J. A. (2018) · Genome biology · doi:10.1186/s13059-018-1598-7 · Cited by 50
Chromatin folding and nuclear architecture: PRC1 function in 3D
Illingworth, R. S. (2019) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2019.06.006 · Cited by 50
Lipiński, M., Muñoz‐Viana, R., del Blanco, B., Márquez-Galera, Á., Medrano-Relinque, J., Caramés, J. M., Szczepankiewicz, A. A., Fernández‐Albert, J., Navarrón, C. M., Olivares, R., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16246-0 · Cited by 55
D’Incal, C. P., Rossem, K. E. V., Man, K. D., Konings, A., Dijck, A. V., Rizzuti, L., Vitriolo, A., Testa, G., Gozes, I., Berghe, W. V., et al. (2023) · Clinical Epigenetics · doi:10.1186/s13148-023-01450-8 · Cited by 52
HiCDB: a sensitive and robust method for detecting contact domain boundaries
Chen, F., Li, G., Zhang, M. Q., & Chen, Y. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky789 · Cited by 45
“While our paper was in preparation, a separate group reported an ultra-high-resolution Hi-C map of mouse neural differentiation and independently confirmed that the local insulation correlates to active transcription by inspecting the insulation changes at gene promoters (49).”
BackgroundBianchi, A., Mozzetta, C., Pegoli, G., Lucini, F., Valsoni, S., Rosti, V., Petrini, C., Cortesi, A., Gregoretti, F., Antonelli, L., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci128161 · Cited by 49
“We verified that the PPARG locus is included in a TAD encompassing a region extending also upstream of the PPARG locus itself, using high-resolution Hi-C data on mouse embryonic stem cells (35) and the 3D Genome Browser (36) (Figure S10).”
MethodPHi-C: deciphering Hi-C data into polymer dynamics
Shinkai, S., Nakagawa, M., Sugawara, T., Togashi, Y., Ochiai, H., Nakato, R., Taniguchi, Y., & Onami, S. (2020) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqaa020 · Cited by 48
“To investigate how PHi-C explains 4D features of chromosomes within living cells, we applied this approach to Hi-C data for mESCs (32).”
MethodStefano, M. D., Nützmann, H., Martı́-Renom, M. A., & Jost, D. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa1275 · Cited by 48
“In eukaryotic cells, the genome structure is characterized by a complex three-dimensional (3D) organization (1–3) that plays a crucial role in regulating gene function and expression (4, 5), and in determining cell-fate decisions (6–9), and cell-development (6, 10).”
BackgroundUltra-long-range interactions between active regulatory elementsPreprint
Friman, E. T., Flyamer, I. M., Marenduzzo, D., Boyle, S., & Bickmore, W. A. (2023) · Genome Research · doi:10.1101/gr.277567.122 · Cited by 51
“In mouse embryonic stem cells (mESCs) and differentiated cell types, active transcription start sites (TSSs) and transcription factor (TF) binding sites have been shown to interact with their own type across 2 – 10 Mb (Bonev et al. 2017).”
BackgroundMethodInfluentialMagli, A., Baik, J., Pota, P., Cordero, C. O., Kwak, I.-Y., Garry, D. J., Love, P. E., Dynlacht, B. D., & Perlingeiro, R. C. R. (2019) · Nature Communications · doi:10.1038/s41467-019-10318-6 · Cited by 47
Pei, L., Huang, X., Liu, Z., Tian, X., You, J., Li, J., Fang, D. D., Lindsey, K., Zhu, L., Zhang, X., et al. (2022) · Genome biology · doi:10.1186/s13059-022-02616-y · Cited by 50
DNA sequence-dependent formation of heterochromatin nanodomains
Thorn, G. J., Clarkson, C. T., Rademacher, A., Mamayusupova, H., Schotta, G., Rippe, K., & Teif, V. B. (2022) · Nature Communications · doi:10.1038/s41467-022-29360-y · Cited by 49
Pereira, A., Diwakar, J., Masserdotti, G., Beşkardeş, S., Simon, T., So, Y., Martín-Loarte, L., Bergemann, F., Vasan, L., Schauer, T., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01677-5 · Cited by 52
Self-citationEpigenetic and Transcriptional Pre-patterning—An Emerging Theme in Cortical Neurogenesis
Albert, M., & Huttner, W. Β. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00359 · Cited by 53
“During neural differentiation, both in vitro and in the mouse developing neocortex, chromatin interactions change dynamically, frequently related to neural transcription factors that contribute to chromosome reorganization (Bonev et al., 2017).”
Backgroundα1ACT Is Essential for Survival and Early Cerebellar Programming in a Critical Neonatal Window
Du, X., Wei, C., Pastor, D. P. H., Rao, E. R., Li, Y., Grasselli, G., Godfrey, J. D., Palmenberg, A. C., Andrade, J., Hansel, C., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.036 · Cited by 49
Viewing Nuclear Architecture through the Eyes of Nocturnal Mammals
Feodorova, Y. N., Falk, M. J., Mirny, L. A., & Solovei, I. V. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.12.008 · Cited by 52
Wang, J., Wang, J., Yang, L., Zhao, C., Wu, L.-M. N., Xu, L., Zhang, F., Weng, Q., Wegner, M., & Lu, Q. R. (2020) · Nature Communications · doi:10.1038/s41467-020-17955-2 · Cited by 48
3D genome evolution and reorganization in the Drosophila melanogaster species group
Torosin, N. S., Anand, A., Golla, T. R., Cao, W., & Ellison, C. E. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1009229 · Cited by 46
“For example, genome-wide enhancer-promoter contacts in mouse neurons occur mainly within TADs [14] and reporter gene-enhancer interactions have been shown to be correlated with TAD structure [15].”
BackgroundSingle-cell Hi-C data analysis: safety in numbers
Galitsyna, A. A., & Gelfand, M. S. (2021) · Briefings in Bioinformatics · doi:10.1093/bib/bbab316 · Cited by 47
“This number is two orders of magnitude lower than bulk Hi-C (around 1700 contacts per 1Kb or genome in neural progenitor cells [7]).”
BackgroundThe role of insulators and transcription in 3D chromatin organization of fliesPreprint
Chathoth, K. T., Mikheeva, L. A., Crevel, G., Wolfe, J. C., Hunter, I., Beckett-Doyle, S., Cotterill, S., Dai, H., Harrison, A., & Zabet, N. R. (2022) · Genome Research · doi:10.1101/gr.275809.121 · Cited by 46
“scription using the CRISPR-Cas9 system in mouse neuronal progenitor cells was not sufficient to induce TAD boundary formation (Bonev et al. 2017).”
Evolution of 3D chromatin organization at different scales
Acemel, R. D., & Lupiáñez, D. G. (2023) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2022.102019 · Cited by 50
Salari, H., Stefano, M. D., & Jost, D. (2021) · Genome Research · doi:10.1101/gr.275827.121 · Cited by 45
“Dataset GEO accession Organism Cell type Restriction enzyme Runs Reference genome (Bonev et al. 2017) GSM2533818 Mus musculus mESC (E14) DpnII 14 mm10”
BackgroundMethodInfluentialNiu, C., Wang, S., Guo, J., Wei, X., Jia, M., Chen, Z., Gong, W., Qin, Y., Wang, X., Zhi, X., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab034 · Cited by 45
“In order to test this hypothesis, we used published HiC data in mESCs (34) and found that these regions indeed formed chromatin loops with the BACH1 bound sites (Figure 5A and B, Supplemental Figure S7D).”
MethodCollective regulation of chromatin modifications predicts replication timing during cell cycle
Rechem, C. V., Ji, F., Chakraborty, D., Black, J. C., Sadreyev, R. I., & Whetstine, J. R. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109799 · Cited by 48
“Insulation scores were calculated as previously described (Bonev et al., 2017).”
Ji, H. Y., Uyan, Ö., Yan, K., Liu, T., Zhu, Q., Tóthová, Z., Botten, G. A., Xu, J., Yuan, G., Dekker, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26574-4 · Cited by 49
Making sense of the linear genome, gene function and TADs
Long, H., Greenaway, S., Powell, G., Mallon, A., Lindgren, C. M., & Simon, M. M. (2022) · Epigenetics & Chromatin · doi:10.1186/s13072-022-00436-9 · Cited by 52
“In order to test this hypothesis, we utilised some of the highest quality mammalian Hi-C data currently in the public domain [25] and annotated TADs using two TAD calling algorithms; Arrowhead and TopDom [23, 24].”
MethodInfluentialMurphy, S. E., & Boettiger, A. N. (2024) · Nature Genetics · doi:10.1038/s41588-024-01661-6 · Cited by 53
“5, we manually curated a set of 36 H3K27me3 contact interactions (sometimes called Polycomb loops) using published Hi-C and ChIP–seq data from mouse cortical neurons 18 .”
InfluentialYou, Q., Cheng, A. Y., Gu, X., Harada, B. T., Yu, M., Wu, T., Ren, B., Ouyang, Z., & He, C. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0643-8 · Cited by 46
Metadata
- Authors
- Bonev, B., Mendelson Cohen, N., Szabo, Q., Fritsch, L., Papadopoulos, G. L., Lubling, Y., Xu, X., Lv, X., Hugnot, J.-P., Tanay, A., & Cavalli, G.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Weizmann Institute of Science (IL)
- BGI Group (China) (CN)
- Inserm (FR)
- Corresponding author
- Bonev, Boyan
- Cavalli, Giacomo
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 171
- Issue
- 3
- Pages
- 557-572.e24
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5651218
- OpenAlex
- W2765567136
- Semantic Scholar
- 0728437b5553338297a6cc1bad9f15766a1e1c43
- Cited by
- 1,338
- References
- 53
- Citations by year
- 2026: 110 · 2025: 129 · 2024: 143 · 2023: 139 · 2022: 166 · 2021: 181 · 2020: 190 · 2019: 170 · 2018: 100 · 2017: 6
- FWCI
- 52.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Funders
- European Research Council (232947)
- Israeli Science Foundation
- CNRS
- FP7 European Network of Excellence EpiGeneSys (676556)
- Agence Nationale de la Recherche (ANR-15-CE12-006-01)
- Fondation pour la Recherche Médicale (144186)
- INSERM and ITMO Cancer (PLBIO16-22)
- Laboratory of Excellence (ANR-10-LABX-12-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- 3D genome organization, chromatin conformation, neuronal differentiation, topologically associating domains, long-range chromatin interactions, chromatin insulation, enhancer-promoter interactions
- MeSH terms
- CCCTC-Binding Factor, Animals, Chromatin, Enhancer Elements, Genetic, Exons, Promoter Regions, Genetic, Repressor Proteins, Transcription Factors, Gene Expression, Genome, Mice, Gene Regulatory Networks, Embryonic Stem Cells, Neurogenesis
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