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Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization
Open accessPublished version of a preprint
Abstract
Summary The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding. CTCF remains essential for TAD organization in non-dividing cells. Surprisingly, active and inactive genome compartments remain properly segregated upon CTCF depletion, revealing that compartmentalization of mammalian chromosomes emerges independently of proper insulation of TADs. Further, our data support that CTCF mediates transcriptional insulator function through enhancer-blocking but not as a direct barrier to heterochromatin spreading. Beyond defining the functions of CTCF in chromosome folding these results provide new fundamental insights into the rules governing mammalian genome organization.
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TL;DR
Acute auxin-inducible degradation of CTCF in mouse embryonic stem cells shows that CTCF is required for CTCF-site looping and TAD insulation but not for A/B compartmentalization. The paper separates local TAD insulation from higher-order genome compartmentalization and supports CTCF as an enhancer blocker rather than a direct H3K27me3 barrier.
Key findings
- CTCF depletion abolished CTCF-anchored loops and caused loss of insulation at >80% of TAD boundaries; 1000 persistent CTCF-less boundaries (18% of initial boundaries) remained, and restoring CTCF re-established architecture.
- A/B compartments remained properly segregated after CTCF depletion, with only a minor reproducible ~10% reduction in compartmentalization strength; contact-frequency scaling with genomic distance did not change.
- Insulation defects were dose-dependent: cells with around 15% residual CTCF preserved more insulation than completely depleted cells, helping explain milder RNAi phenotypes that leave 10–15% CTCF.
- RNA-seq showed 370 differentially expressed genes at day 1 and 4996 at day 4; >80% of early down-regulated genes had CTCF bound within 1 kb of the TSS, while up-regulated genes were closer to active enhancers and more often separated from them by a TAD boundary. CTCF depletion did not trigger H3K27me3 spreading.
Methods
- Endogenous CTCF was tagged at both Ctcf alleles with an auxin-inducible degron (AID) in E14Tg2a mouse embryonic stem cells, with Tir1 expression and 500 µM auxin/IAA for acute, reversible depletion; cells were also differentiated into neural precursor cells and resting astrocytes.
- Chromosome conformation was assayed by 5C at the Xic and by Hi-C at 20 kb/100 kb resolution, alongside ChIP-seq, ChIP-exo, RNA-seq time courses, 3D DNA FISH, Western blotting, flow cytometry, and proliferation assays.
- Analyses included insulation-score boundary calling, A/B compartment eigenvector analysis, differential expression, CTCF motif orientation, and integration with CTCF/Cohesin loop anchors and enhancer annotations.
Limitations
- The paper states that comparing Hi-C and FISH is limited because Hi-C read numbers are normalized between samples while FISH distances are absolute; it also notes that RNA-seq does not directly measure ongoing transcription rates and that limited Hi-C resolution prevents robust identification of small TADs.
- The paper states that Tir1 transgene variegation upon differentiation limited analyses in committed cells, that CTCF-AID NPC subclones did not survive freeze-thawing, and that insulation did not reform after auxin washout in resting astrocytes.
- The text makes evident that most experiments rely on mESCs and selected loci/cell types, that the AID fusion caused basal CTCF levels about 2–3-fold lower than parental cells, and that prolonged depletion produces secondary effects, so the study focuses on acute depletion during at least two days.
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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
“Surprisingly, active and inactive genome compartments remain properly segregated upon CTCF depletion, revealing that compartmentalization of mammalian chromosomes emerges independently of proper insulation of TADs.”
- Also stated in: § Disruption of Local Insulation Does Not Affect Higher-Order Chromosome Folding · hedged
“Contact maps (Figure 4A) as well as compartment signal (Imakaev et al., 2012) indicated that compartmentalization and genomic location of the transitions between A-and B- compartments are maintained after CTCF depletion (Figure 4B-C and S4A).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Abstract
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In the paper
“The fact that in our data CTCF does not bind the majority (80%) of TSS of genes up-regulated after 1 day suggests CTCF normally represses them indirectly.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > CTCF and transcriptional regulation
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In the paper
“We detected a minor but reproducible reduction (∼10%) in the strength of compartmentalization upon CTCF depletion (Figure S4B).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > Disruption of Local Insulation Does Not Affect Higher-Order Chromosome Folding
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In the paper
“Taking advantage of the Smc1a HiChIP data we noticed that promoters of mis-regulated genes are more often close to loop anchors than promoters of non-regulated genes (Figure S6D), while the distribution is similar outside of the anchors.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > CTCF and transcriptional regulation
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In the paper
“Strikingly, the orientation of the CTCF motif at these TSSs is almost systematically in direct orientation with the direction of transcription (90% of unequivocal sites, Figure 6C and Supplementary Table 7).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > CTCF and transcriptional regulation
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“consistent with previous boundary-deletion experiments (Ji et al., 2016), TAD boundaries separate further apart in the three-dimensional space of the nucleus (Figure S3L).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > CTCF Depletion Triggers Dramatic Loss of TAD Insulation
What the sources say
- Not checked yetcites Ji et al., 2016
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In the paper
“Intra-TAD FISH distances were unaffected by CTCF depletion, indicating that loss of CTCF does not trigger general chromatin compaction.”
- Also stated in: § CTCF Binding Is Not a Direct Impediment to H3K27me3 Spreading in mESCs · plain
“Overall chromosome compaction and organization are however not affected.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > CTCF Depletion Triggers Dramatic Loss of TAD Insulation
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In the paper
“The enrichment level in persistent peaks was severely reduced (Figure S2D-E), indicating that CTCF occupancy is lost or considerably lower at all of its binding sites after depletion.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > Auxin Treatment Severely Depletes CTCF from Chromatin
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In the paper
“From these 1000 CTCF-less residual boundaries 609 (61%) had at least one CTCF ChIP-seq peak +/- 1 bin (20kb) prior to depletion, suggesting that CTCF binding at these sites is not what initially drove local insulation.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > Disruption of Local Insulation Does Not Affect Higher-Order Chromosome Folding
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“As reported previously the AID fusion led to slight constitutive destabilization (Morawska and Ulrich, 2013), so that basal CTCF levels were about 2–3-fold less in the AID-eGFP fusion line compared to the untagged parental line (Figure 1B and C).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > Acute CTCF Depletion with the Auxin-Inducible Degron System
What the sources say
- Not checked yetcites Morawska and Ulrich, 2013
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- It may state two separate claims as one. 24
- Probably not a substantial claim. 23
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
“After removing those that displayed residual CTCF binding by ChIP-seq we identified 1000 persistent CTCF-less boundaries (18% of initial boundaries), where insulation was much less affected by CTCF depletion (Figure 3B).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > CTCF Depletion Triggers Dramatic Loss of TAD Insulation
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In the paper
“Integration with CTCF Chip-exo data revealed that over 80% of the early down-regulated genes had CTCF bound within 1kb of the transcription start site (TSS) prior to depletion, as opposed to less than 20% of the up-regulated genes (Figure 6B).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > CTCF and transcriptional regulation
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In the paper
“Washing off auxin led to reformation of insulated TADs in mESCs and NPCs but not resting astrocytes.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > Loss of CTCF also Triggers Misfolding in Non-Cycling Cells
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In the paper
“Auxin washoff after a 2-day treatment did not completely restore the transcriptome, with most (252 out of 278, 90%) of the differentially expressed genes remaining up-regulated compared to untreated cells (Figure 6A-B).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > CTCF and transcriptional regulation
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In the paper
“with around half of the dysregulated being down-regulated and half up-regulated at each time-point.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > CTCF and transcriptional regulation
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In the paper
“CTCF depletion was maximal as early as 3h45 after adding auxin (Figure 1E).”
- Also stated in: § Acute CTCF Depletion with the Auxin-Inducible Degron System · plain
“Recovery initiated readily after washoff and was half complete by 15h (Figure 1E).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > Acute CTCF Depletion with the Auxin-Inducible Degron System
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Acute CTCF Depletion with the Auxin-Inducible Degron System · 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
“Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding.”
- Also stated in: § CTCF is required for accumulating chromatin loops at CTCF sites · plain
“In contrast, auxin-mediated depletion of CTCF led to complete disappearance of these 5C peaks while auxin washoff restored them (Figure S2I).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § CTCF is required for accumulating chromatin loops at CTCF sites · plain
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In the paper
“Importantly, CTCF depletion in mESCs did not block cells in a specific phase of the cell cycle, and did not induce DNA damage or aneuploidy (Supplementary figures 1D-E).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > Acute CTCF Depletion with the Auxin-Inducible Degron System
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In the paper
“Folding defects appeared somewhat less pronounced in differentiated cells, correlating with switching of a large portion of the region surveyed into a lamina associated domain (LAD) – and presumably B compartment (Figure 5A-D).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > Loss of CTCF also Triggers Misfolding in Non-Cycling Cells
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In the paper
“In contrast, auxin-mediated degradation of CTCF prevented subcloning of CTCF-AID cells, recapitulating the full CTCF knockout phenotype in mESCs (Sleutels et al., 2012) (Figure 1D).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > Acute CTCF Depletion with the Auxin-Inducible Degron System
What the sources say
- Not checked yetcites Sleutels et al., 2012 source
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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
“Loss of CTCF led to loss of insulation at most boundaries (>80%, Figure 3B).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > CTCF Depletion Triggers Dramatic Loss of TAD Insulation
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In the paper
“We noticed that at the promoter of the immediately down-regulated genes CTCF is bound slightly upstream of the TSS (around 60bp) and demarcates the beginning of the nucleosome-depleted region (Figure 6C).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > CTCF and transcriptional regulation
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In the paper
“On a more global scale, we observed a slight but significant decrease in overall H3K27me3 levels (Figure S7B).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > CTCF Binding Is Not a Direct Impediment to H3K27me3 Spreading in mESCs
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In the paper
“Auxin in itself was neutral to untagged mESCs (Figure 1D and E), with no differential gene activity detected after up to 4 days of treatment (Supplementary tables 2 and 3).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > Acute CTCF Depletion with the Auxin-Inducible Degron System
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In the paper
“Basal CTCF-AID-eGFP levels were slightly lower (1.5-2 fold) than when Tir1 was inserted at Rosa26 or randomly (Figure S3C)”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Gene targeting
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In the paper
“We observed equivalent CTCF depletion efficiency with the AID* as with the original full-length 231 amino-acid tag (Nishimura et al., 2009) (data not shown).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Plasmid Construction
What the sources say
- Not checked yetcites Nishimura et al., 2009 source
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In the paper
“The Tir1 transgene variegated upon differentiation, which we overcame by first converting CTCF-AID mESCs into self-renewing Neural Precursor Cells (NPCs), subcloning NPCs and then selecting clonal lines that retained homogenous CTCF degradation upon auxin treatment.”
- Also stated in: § Gene targeting · plain
“Indeed our CTCF-AID lines down-regulated Tir1 during differentiation, even when targeted at Rosa26, leading to variegation of auxin response and limiting our analyses in committed cells that can be subcloned, such as neural progenitors.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Experimental Model and Subject Details > Neural progenitor cells and astrocytes
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- Also stated in: § Gene targeting · plain
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In the paper
“We noticed that only a handful of resistant clones were recovered, suggesting sub-optimal targeting – either because of the sgRNA or the targeting construct.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Gene targeting
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In the paper
“We noticed that Tir1 targeting with the Tigre targeting vector was at least 5-fold more efficient than with our Rosa26 targeting vector.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Gene targeting
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In the paper
“These changes enable proceeding through the 3C protocol in a single tube per sample, allow handling of over 20 samples in parallel, reduce the amount of cells needed by a factor 5 to 10 and cut down the time needed to complete the protocol from 8 days (Nora et al. 2012) to 4 days.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Chromosome Conformation Capture Carbon-Copy (5C)
What the sources say
- Not checked yetcites Nora et al. 2012 source
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. It may state two separate claims as one.
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In the paper
“We noticed the dual nickase underperformed for Rosa26 and recommend using a single nuclease strategy approach with the first sgRNA only.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Plasmid Construction
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In the paper
“The emerging model is that Cohesin packages the chromatin fiber while CTCF defines focal boundaries by constrains this packaging activity.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Discussion > TAD Insulation and Transcriptional Regulation
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In the paper
“While this is compatible with compartment transition or transcription participating in the maintenance of CTCF-independent insulation, either of these features alone is not sufficient to drive CTCF-independent insulation since most boundaries associated with them are affected by CTCF depletion (Supplementary Table 6).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > Disruption of Local Insulation Does Not Affect Higher-Order Chromosome Folding
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In the paper
“Notably, the extrusion model accurately describes mammalian chromosome folding at the sub-megabase scale but does not account for the segregation of genomic compartments, and the direct molecular drivers of CTCF-independent higher-order compartmentalization remain to be defined.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Discussion > Local Insulation and A/B Compartmentalization Are Molecularly Separable Principles of Mammalian Genome Folding
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In the paper
“This would explain why depleting CTCF does not affect how the frequency of chromosomal contacts scales overall with genomic distance, as opposed to altering factors that control Cohesin turnover on chromatin, such as Nipbl (Schwarzer et al., 2016).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Discussion > TAD Insulation and Transcriptional Regulation
What the sources say
- Not checked yetcites Schwarzer et al., 2016
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In the paper
“These changes are likely indirect effects as they are not restricted to the vicinity of CTCF sites, and may be accounted for by 2-fold transcriptional down-regulation of the essential PRC2 component EED (Supplementary Table 3).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Results > CTCF Binding Is Not a Direct Impediment to H3K27me3 Spreading in mESCs
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In the paper
“The relative efficiency of Hi-C ligation product formation and biotin fill-in was defined as the proportion of ligation product digested with NheI and varied from 50 to 80% in different Hi-C libraries.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Hi-C
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In the paper
“this analysis suggested the optimal threshold of 0.3, where the specificity of loop anchor recall dropped 3-fold.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Quantification and Statistical Analysis > Hi-C analysis
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In the paper
“It indicated that the majority of the ligation products have been digested by NheI and validated that the libraries were mainly constituted of true ligation products.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Hi-C
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In the paper
“Over 95% of cells had one knock-in allele, of which 20% were homozygous.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Gene targeting
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In the paper
“Rosa26 PCR genotyping revealed this clone had undergone random insertion of the Tir1 cassette.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Gene targeting
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In the paper
“The clone analyzed here was homozygous for the integration and the puro cassette was still present in the final cell line.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Plasmid Construction
Strength:plain· not yet calibratedSingle caseTests✓ 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.
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
“Dissociation, wahs and Flow buffers were supplemented with auxin, when appropriate, to avoid re-expression of the CTCF-AID-eGFP fusion.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Flow Cytometry
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
“Negative controls (no ligase, no template, no 5C oligonucleotide) were included during each experiments to ensure the absence of contamination.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Chromosome Conformation Capture Carbon-Copy (5C)
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.
In the paper
“For peak calling we followed the guidelines described in (Thomas et al., 2016).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Quantification and Statistical Analysis > ChIP-seq Analysis
What the sources say
- Not checked yetcites Thomas et al., 2016 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.
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
“The CTCF-AID NPC subclones did not survive freeze and thawing.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Experimental Model and Subject Details > Neural progenitor cells and astrocytes
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.
None of the sources cited for this claim have been checked yet.
In the paper
“We used the smallest functional truncation of the AID tag (AID*, 44 amino-acids), initially developed in yeast (Morawska and Ulrich, 2013), shorter than the mini-AID (67 amino-acids (Kubota et al., 2013)).”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Plasmid Construction
What the sources say
- Not checked yetcites Morawska and Ulrich, 2013
- Not checked yetcites Kubota et al., 2013 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.
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
“Half of the clones were found to have undergone FlpO-mediated recombination. When homozygous both alleles always underwent recombination.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Gene targeting
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.
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
“The consensus peak list was obtained by retaining peaks that overlapped for at least 1bp between biological replicates.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Quantification and Statistical Analysis > ChIP-seq Analysis
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
“FPKM provided in Supplementary Table 3 are means from 3 independent biological replicates.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Quantification and Statistical Analysis > RNA-seq Analysis
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 selected the clone with the fewest GFP-positive cells (<1%) after 24h of auxin treatment.”
§ Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization > Method Details > Gene targeting
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
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
“Depleting RAD21 or CCCTC-binding factor (CTCF) also down-regulated Car2 (fig. S12C) (7, 30)”
From Synergy between regulatory elements can render cohesin dispensable for distal enhancer function (2026) · cites this paper as [30]
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
“Finally, the temporary disruption of 3D loops on a genome-wide scale through cohesin depletion was found to have minimal lasting effect on gene expression155,156.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [156]
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
“Surprisingly however, deletion or degradation of cohesin or CTCF in differentiated cells has only mild effects on gene expression [344–349].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [346]
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
“The A/B compartment structure does not disappear (and is in fact even strengthened) upon cohesin/CTCF depletion [344, 346–348], but, like TADs, dissolves in mitosis [459].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [346]
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
“rapid depletion of cohesin or CTCF quickly abolishes TADs but, as mentioned above, has only relatively mild effects on gene expression [301, 345–347, 448].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [346]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“Convergent binding sites for the versatile transcription factor CTCF (CCCTC-binding factor) located at TAD borders [46] block the movement of loop extruders [47,48,49].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [47]
In the citing paper
“Our data is consistent with a previous report that genome compartmentalization is preserved after depletion of cohesin (Seitan et al., 2013) or CTCF (Nora et al., 2017).”
From Cohesin Loss Eliminates All Loop Domains (2017) · cites this paper as Nora et al., 2017
In the citing paper
“Our data for cohesin depletion is consistent with is study.”
From Cohesin Loss Eliminates All Loop Domains (2017) · cites this paper as Nora et al., 2017
In the citing paper
“loop extrusion mediated by cohesin and CTCF mediates the formation of chromatin loops and self-interacting Topologically Associating Domains (TADs)”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [86]
In the citing 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).”
From Multiscale 3D Genome Rewiring during Mouse Neural Development (2017) · cites this paper as Nora et al., 2017
In the citing 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)”
From Multiscale 3D Genome Rewiring during Mouse Neural Development (2017) · cites this paper as Nora et al., 2017
In the citing paper
“complementary polymer simulation studies and Hi-C studies employing acute depletion of CTCF and cohesin, which also support such a dynamic model.”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [10]
In the citing paper
“Finally, ∼18% of TAD boundaries appear to be partially resistant to CTCF loss,10 suggesting that additional boundary factors, such as active promoters4 since engaged RNA Pol II can block cohesin extrusion46 as well as alternative architectural factors, may also play a role.”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [10]
In the citing paper
“Likewise, CTCF loss has only a small effect on epigenomic compartments,10 whereas cohesin loss increases the degree of epigenomic compartmentalization ∼2-fold.11,13”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [10]
In the citing paper
“In conclusion, recent studies10–15 employing induced CTCF and cohesin degradation now strongly support a model where cohesin forms TADs and CTCF establishes TAD boundaries.”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [10]
In the citing paper
“Consistent with their different roles, CTCF loss has essentially no effect on genome-averaged contact probability at any distance scale,10 whereas cohesin loss significantly reduces contact probability at the scale of tens to hundreds of kilobases,11”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [10]
In the citing paper
“In accordance with the extrusion model, TADs and well-defined Hi-C loops largely disappear when either CTCF10,14 or cohesin11,13–15 is strongly depleted, but for different reasons.”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [10]
In the citing paper
“In summary, CTCF and cohesin are required for chromatin looping,10–15 form a biochemically stable protein-complex and both bind chromatin at loop anchors.”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [10]
In the citing paper
“Thus, chromatin is still compacted and extruded by cohesin, but without sharp boundaries, TADs disappear in Hi-C maps.10,14”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [10]
In the citing paper
“Since multiple studies show that TADs and chromatin loops disappear without CTCF10,14 and cohesin,11,13–15 we reasoned that the most stable protein of CTCF and cohesin should set an upper limit on the stability of TADs and chromatin loops.”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [10]
In the citing paper
“although CTCF and cohesin both appear absolutely required for the formation of most TADs10-15”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [10]
In the citing paper
“Notably, a key advantage of dynamic loop extrusion models is that they can explain recent perturbation experiments where CTCF binding sites have been added or deleted9,49-51 and also explain the loss of either CTCF or cohesin.10-15”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [10]
In the citing paper
“(∼18% of TAD boundaries were not sensitive to CTCF loss10 and could have different dynamics)”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [10]
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.
RecJf digestion step specifies lambda exonuclease
MinorThe step is described as RecJf exonuclease digestion and uses RecJf buffer, but the enzyme specified for that step is lambda exonuclease.
“RecJf exonuclease digestion was performed by resuspending the beads in 100μL 1× RecJf exonuclease buffer”
“supplemented with 30U lambda exonuclease (NEB) and incubating at 37°C for 30min.”
CTCF tag placement differs between Results and Methods
MinorThe Results say the AID-eGFP tag was introduced at the Ctcf stop codon, but the gene-targeting Methods say it was knocked in at the N-terminus of CTCF.
“we targeted the stop codon of both Ctcf alleles to introduce a 44–amino acid version of the AID tag”
“To knock in the AID-eGFP cassette at the N-terinus of CTCF E14Tg2a passage 19 were transfected by microporation”
Different Tir1 targeting vectors specified for cell line #1
MinorThe plasmid-construction Methods identify pEN113 as the Tir1 vector for cell line #1, whereas the gene-targeting Methods say pEN114 was used to introduce Tir1 into the line subsequently identified as #1.
“The Tir1 expression vector (pEN113) for the cell line analyzed by Hi-C (#1) was assembled”
“To knock in the Tir1-expressing cassette one homozygous CTCF-AID-eGFP clone was transfected as described above using a 100μL tip format and pEN114 as the targeting construct.”
Citations
Cites
NIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., & Pachter, L. (2010) · Nature Biotechnology · doi:10.1038/nbt.1621 · Cited by 15,556
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
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
Self-citationTopological 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
FIMO: scanning for occurrences of a given motif
Grant, C. E., Bailey, T. L., & Noble, W. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr064 · Cited by 4,247
Flagged first, then by citations
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Sorted by citations
Cohesin Loss Eliminates All Loop Domains
Rao, S. S. P., Huang, S.-C., Glenn St Hilaire, B., Engreitz, J. M., Perez, E. M., Kieffer-Kwon, K.-R., Sanborn, A. L., Johnstone, S. E., Bascom, G. D., Bochkov, I. D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.026 · Cited by 1,883
“Our data is consistent with a previous report that genome compartmentalization is preserved after depletion of cohesin (Seitan et al., 2013) or CTCF (Nora et al., 2017).”
BackgroundResultMultiscale 3D Genome Rewiring during Mouse Neural Development
Bonev, B., Mendelson Cohen, N., Szabo, Q., Fritsch, L., Papadopoulos, G. L., Lubling, Y., Xu, X., Lv, X., Hugnot, J.-P., Tanay, A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.043 · Cited by 1,338
Organizational principles of 3D genome architecture
Rowley, M. J., & Corces, V. G. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0060-8 · Cited by 1,171
Two independent modes of chromatin organization revealed by cohesin removal
Schwarzer, W., Abdennur, N., Goloborodko, A., Pekowska, A., Fudenberg, G., Loe-Mie, Y., Fonseca, N. A., Huber, W., Haering, C. H., Mirny, L., et al. (2017) · Nature · doi:10.1038/nature24281 · Cited by 1,196
Self-citationLong-range enhancer–promoter contacts in gene expression control
Schoenfelder, S., & Fraser, P. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0128-0 · Cited by 1,102
YY1 Is a Structural Regulator of Enhancer-Promoter Loops
Weintraub, A. S., Li, C. H., Zamudio, A. V., Sigova, A. A., Hannett, N. M., Day, D. S., Abraham, B. J., Cohen, M. A., Nabet, B., Buckley, D. L., et al. (2017) · Cell · doi:10.1016/j.cell.2017.11.008 · Cited by 992
“These results were comparable to the effects observed with the rescue of CTCF-CTCF interactions in a similar experiment described recently (Figures 7F and S7C) (Nora et al., 2017), and support the model that YY1 contributes to structuring of a large fraction of enhancer-promoter loops genome-wide.”
High-resolution TADs reveal DNA sequences underlying genome organization in flies
Ramírez, F., Bhardwaj, V., Arrigoni, L., Lam, K. C., Grüning, B. A., Villaveces, J. M., Habermann, B. H., Akhtar, A., & Manke, T. (2018) · Nature Communications · doi:10.1038/s41467-017-02525-w · Cited by 993
Wutz, G., Várnai, C., Nagasaka, K., Cisneros, D. A., Stocsits, R. R., Tang, W., Schoenfelder, S., Jessberger, G., Muhar, M., Hossain, M. J., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201798004 · Cited by 864
A pathway for mitotic chromosome formation
Gibcus, J. H., Samejima, K., Goloborodko, A. A., Samejima, I., Naumova, N., Nuebler, J., Kanemaki, M. T., Xie, L., Paulson, J. R., Earnshaw, W. C., et al. (2018) · Science · doi:10.1126/science.aao6135 · Cited by 744
Self-citationStructural variation in the 3D genome
Spielmann, M., Lupiáñez, D. G., & Mundlos, S. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0007-0 · Cited by 752
The role of 3D genome organization in development and cell differentiation
Zheng, H., & Xie, W. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0132-4 · Cited by 742
Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding
Hsieh, T.-H. S., Cattoglio, C., Slobodyanyuk, E., Hansen, A. S., Rando, O. J., Tjian, R., & Darzacq, X. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.03.002 · Cited by 661
Heterochromatin drives compartmentalization of inverted and conventional nuclei
Falk, M., Feodorova, Y., Naumova, N., Imakaev, M., Lajoie, B. R., Leonhardt, H., Joffe, B., Dekker, J., Fudenberg, G., Solovei, I., et al. (2019) · Nature · doi:10.1038/s41586-019-1275-3 · Cited by 646
Self-citationDevelopmental enhancers and chromosome topology
Furlong, E. E. M., & Levine, M. (2018) · Science · doi:10.1126/science.aau0320 · Cited by 641
Chromatin organization by an interplay of loop extrusion and compartmental segregation
Nuebler, J., Fudenberg, G., Imakaev, M., Abdennur, N. A., & Mirny, L. A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1717730115 · Cited by 638
“Motivated by recent experiments that point toward such an interplay (12, 37), we used polymer models of chromosomes to investigate whether simultaneous action of loop extrusion and compartmental segregation can quantitatively reproduce experimental findings.”
MethodSelf-citationUltrastructural Details of Mammalian Chromosome Architecture
Krietenstein, N., Abraham, S., Venev, S. V., Abdennur, N., Gibcus, J., Hsieh, T.-H. S., Parsi, K. M., Yang, L., Maehr, R., Mirny, L. A., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.03.003 · Cited by 622
Self-citationCTCF and cohesin regulate chromatin loop stability with distinct dynamics
Hansen, A. S., Pustova, I., Cattoglio, C., Tjian, R., & Darzacq, X. (2017) · eLife · doi:10.7554/elife.25776 · Cited by 613
Principles of genome folding into topologically associating domains
Szabo, Q., Bantignies, F., & Cavalli, G. (2019) · Science Advances · doi:10.1126/sciadv.aaw1668 · Cited by 631
The Energetics and Physiological Impact of Cohesin Extrusion
Vian, L., Pękowska, A., Rao, S. S. P., Kieffer-Kwon, K.-R., Jung, S., Baranello, L., Huang, S.-C., El Khattabi, L., Dose, M., Pruett, N., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.072 · Cited by 581
Evolutionarily Conserved Principles Predict 3D Chromatin Organization
Rowley, M. J., Nichols, M. H., Lyu, X., Ando‐Kuri, M., Rivera, S., Hermetz, K. E., Wang, P., Ruan, Y., & Corces, V. G. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.07.022 · Cited by 560
“Recently published studies have examined the role of CTCF in the formation of loops and TADs using an auxin-mediated degradation system in mammals (Kubo et al., 2017; Nora et al., 2017).”
Yesbolatova, A., Saito, Y., Kitamoto, N., Makino‐Itou, H., Ajima, R., Nakano, R., Nakaoka, H., Fukui, K., Gamo, K., Tominari, Y., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19532-z · Cited by 544
Transcription factors and 3D genome conformation in cell-fate decisions
Stadhouders, R., Filion, G. J. P., & Graf, T. (2019) · Nature · doi:10.1038/s41586-019-1182-7 · Cited by 530
Genome folding through loop extrusion by SMC complexes
Davidson, I. F., & Peters, J. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00349-7 · Cited by 531
The structural basis for cohesin–CTCF-anchored loops
Li, Y., Haarhuis, J. H. I., Sedeño Cacciatore, Á., Oldenkamp, R., van Ruiten, M. S., Willems, L., Teunissen, H., Muir, K. W., de Wit, E., Rowland, B. D., et al. (2020) · Nature · doi:10.1038/s41586-019-1910-z · Cited by 459
Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
Gabriele, M., Brandão, H. B., Grosse-Holz, S., Jha, A., Dailey, G. M., Cattoglio, C., Hsieh, T.-H. S., Mirny, L., Zechner, C., & Hansen, A. S. (2022) · Science · doi:10.1126/science.abn6583 · Cited by 506
Self-citationRoles of transposable elements in the regulation of mammalian transcription
Fueyo, R., Judd, J., Feschotte, C., & Wysocka, J. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00457-y · Cited by 451
Chemically induced proximity in biology and medicine
Stanton, B. Z., Chory, E. J., & Crabtree, G. R. (2018) · Science · doi:10.1126/science.aao5902 · Cited by 475
“Recently, auxin-mediated degradation of the transcription factor CTCF (60) has differentiated its roles in local topologically associating domain (TAD) structure from chromosomal-compartment architecture.”
BackgroundTranscription Elongation Can Affect Genome 3D Structure
Heinz, S., Texari, L., Hayes, M. G. B., Urbanowski, M., Chang, M. W., Givarkes, N., Rialdi, A., White, K. M., Albrecht, R. A., Pache, L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.047 · Cited by 453
Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization
Finn, E. H., Pegoraro, G., Brandão, H. B., Valton, A.-L., Oomen, M. E., Dekker, J., Mirny, L., & Misteli, T. (2019) · Cell · doi:10.1016/j.cell.2019.01.020 · Cited by 459
Self-citationNonlinear control of transcription through enhancer–promoter interactions
Zuin, J., Roth, G., Zhan, Y., Cramard, J., Redolfi, J., Piskadlo, E., Mach, P., Kryzhanovska, M., Tihanyi, G., Kohler, H., et al. (2022) · Nature · doi:10.1038/s41586-022-04570-y · Cited by 415
Hsieh, T.-H. S., Cattoglio, C., Slobodyanyuk, E., Hansen, A. S., Darzacq, X., & Tjian, R. (2022) · Nature Genetics · doi:10.1038/s41588-022-01223-8 · Cited by 406
Towards a comprehensive catalogue of validated and target-linked human enhancers
Gasperini, M., Tome, J. M., & Shendure, J. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-019-0209-0 · Cited by 396
Understanding 3D genome organization by multidisciplinary methods
Jerković, I., & Cavalli, G. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00362-w · Cited by 413
A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture
Gassler, J., Brandão, H. B., Imakaev, M., Flyamer, I. M., Ladstätter, S., Bickmore, W. A., Peters, J., Mirny, L. A., & Tachibana, K.-E. K. (2017) · The EMBO Journal · doi:10.15252/embj.201798083 · Cited by 382
“…cohesin colocalizes with CTCF and is associated with TADs and chromatin loops (Wendt et al , 2008; Dixon et al , 2012; Nora et al , 2012; Phillips-Cremins et al , 2013; Rao et al , 2014; Hansen et al , 2017; Nora et al , 2017), which implicated cohesin as a regulator of intra-chromosomal structure.”
BackgroundMethodInfluentialSelf-citationZhang, Y., Li, T., Preißl, S., Amaral, M. L., Grinstein, J. D., Farah, E. N., Destici, E., Qiu, Y., Hu, R., Lee, A. Y., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0479-7 · Cited by 384
Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity
Alexander, J. M., Guan, J., Li, B., Maliskova, L., Song, M., Shen, Y., Huang, B., Lomvardas, S., & Weiner, O. D. (2019) · eLife · doi:10.7554/elife.41769 · Cited by 346
On the existence and functionality of topologically associating domains
Beagan, J. A., & Phillips‐Cremins, J. E. (2020) · Nature Genetics · doi:10.1038/s41588-019-0561-1 · Cited by 381
Stadhouders, R., Vidal, E., Serra, F., Stefano, B. D., Dily, F. L., Quilez, J., Gómez, A., Collombet, S., Berenguer, C., Cuartero, Y., et al. (2018) · Nature Genetics · doi:10.1038/s41588-017-0030-7 · Cited by 362
Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression
Ghavi-Helm, Y., Jankowski, A., Meiers, S., Viales, R. R., Korbel, J. O., & Furlong, E. E. M. (2019) · Nature Genetics · doi:10.1038/s41588-019-0462-3 · Cited by 354
Organization of Chromosomal DNA by SMC Complexes
Yatskevich, S., Rhodes, J., & Nasmyth, K. (2019) · Annual Review of Genetics · doi:10.1146/annurev-genet-112618-043633 · Cited by 349
Simultaneous profiling of 3D genome structure and DNA methylation in single human cells
Lee, D.-S., Luo, C., Zhou, J., Chandran, S., Rivkin, A., Bartlett, A., Nery, J. R., Fitzpatrick, C., O’Connor, C., Dixon, J. R., et al. (2019) · Nature Methods · doi:10.1038/s41592-019-0547-z · Cited by 340
3D Chromatin Architecture of Large Plant Genomes Determined by Local A/B Compartments
Dong, P., Tu, X., Chu, P.-Y., Lü, P., Zhu, N., Grierson, D. S., Du, B., Li, P., & Zhong, S. (2017) · Molecular Plant · doi:10.1016/j.molp.2017.11.005 · Cited by 324
The relationship between genome structure and function
Oudelaar, A. M., & Higgs, D. R. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-020-00303-x · Cited by 304
The epigenetic basis of cellular heterogeneity
Carter, B. C., & Zhao, K. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-00300-0 · Cited by 324
Static and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development
Phanstiel, D. H., Van Bortle, K., Spacek, D., Hess, G. T., Shamim, M. S., Machol, I., Love, M. I., Aiden, E. L., Bassik, M. C., & Snyder, M. P. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.08.006 · Cited by 299
Despang, A., Schöpflin, R., Franke, M., Ali, S., Jerković, I., Paliou, C., Chan, W.-L., Timmermann, B., Wittler, L., Vingron, M., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0466-z · Cited by 321
Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation
Kubo, N., Ishii, H., Xiong, X., Bianco, S., Meitinger, F., Hu, R., Hocker, J. D., Conte, M., Gorkin, D., Yu, M., et al. (2021) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-00539-5 · Cited by 289
Emerging Evidence of Chromosome Folding by Loop ExtrusionPreprint
Fudenberg, G., Abdennur, N. A., Imakaev, M., Goloborodko, A. A., & Mirny, L. A. (2017) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2017.82.034710 · Cited by 298
“For CTCF, cells begin dying after about 4 days of stringent depletion (Nora et al. 2017).”
BackgroundMethodInfluentialSelf-citationControl of DNA replication timing in the 3D genome
Marchal, C., Sima, J., & Gilbert, D. M. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0162-y · Cited by 308
Predicting 3D genome folding from DNA sequence with Akita
Fudenberg, G., Kelley, D. R., & Pollard, K. S. (2020) · Nature Methods · doi:10.1038/s41592-020-0958-x · Cited by 300
Deciphering the multi-scale, quantitative cis-regulatory code
Kim, S., & Wysocka, J. (2023) · Molecular Cell · doi:10.1016/j.molcel.2022.12.032 · Cited by 302
Early metazoan cell type diversity and the evolution of multicellular gene regulation
Sebé-Pedrós, A., Chomsky, E., Pang, K., Lara‐Astiaso, D., Gaiti, F., Mukamel, Z., Amit, I., Hejnol, A., Degnan, B. M., & Tanay, A. (2018) · Nature Ecology & Evolution · doi:10.1038/s41559-018-0575-6 · Cited by 301
TADs are 3D structural units of higher-order chromosome organization in Drosophila
Szabo, Q., Jost, D., Chang, J., Cattoni, D. I., Papadopoulos, G. L., Bonev, B., Sexton, T., Gurgo, J., Jacquier, C., Nöllmann, M., et al. (2018) · Science Advances · doi:10.1126/sciadv.aar8082 · Cited by 285
Beyond the RNA-dependent function of LncRNA genes
Ali, T., & Grote, P. (2020) · eLife · doi:10.7554/elife.60583 · Cited by 282
Distinct Classes of Chromatin Loops Revealed by Deletion of an RNA-Binding Region in CTCF
Hansen, A. S., Hsieh, T.-H. S., Cattoglio, C., Pustova, I., Saldaña-Meyer, R., Reinberg, D., Darzacq, X., & Tjian, R. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.07.039 · Cited by 279
RNA Interactions Are Essential for CTCF-Mediated Genome Organization
Saldaña-Meyer, R., Rodriguez-Hernaez, J., Escobar, T. M., Nishana, M., Jácome-López, K., Nora, E. P., Bruneau, B. G., Tsirigos, A., Furlan-Magaril, M., Skok, J. A., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.08.015 · Cited by 299
“We then sorted the successfully infected cells (mCherry positive and GFP negative; Figure 2B) to obtain a pooled population of steady-state rescues after degradation of the endogenous CTCF protein via AID (Figures 2B and S2A).”
BackgroundMethodResultInfluentialSelf-citationRecent evidence that TADs and chromatin loops are dynamic structures
Hansen, A. S., Cattoglio, C., Darzacq, X., & Tjian, R. (2018) · Nucleus · doi:10.1080/19491034.2017.1389365 · Cited by 266
Cohesin and CTCF control the dynamics of chromosome folding
Mach, P., Kos, P. I., Zhan, Y., Cramard, J., Gaudin, S., Tünnermann, J., Marchi, E., Eglinger, J., Zuin, J., Kryzhanovska, M., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01232-7 · Cited by 269
Self-citationIntrinsic Dynamics of a Human Gene Reveal the Basis of Expression Heterogeneity
Rodriguez, J., Ren, G., Day, C. R., Zhao, K., Chow, C. C., & Larson, D. R. (2018) · Cell · doi:10.1016/j.cell.2018.11.026 · Cited by 262
Mammalian ISWI and SWI/SNF selectively mediate binding of distinct transcription factors
Barišić, D., Stadler, M. B., Iurlaro, M., & Schübeler, D. (2019) · Nature · doi:10.1038/s41586-019-1115-5 · Cited by 277
Region Capture Micro-C reveals coalescence of enhancers and promoters into nested microcompartments
Goel, V. Y., Huseyin, M. K., & Hansen, A. S. (2023) · Nature Genetics · doi:10.1038/s41588-023-01391-1 · Cited by 271
Ren, G., Jin, W., Cui, K., Rodrigez, J., Hu, G., Zhang, Z., Larson, D. R., & Zhao, K. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.08.026 · Cited by 265
“Our study provides an alternative explanation for those recent findings that targeted degradation of CTCF and/or Cohesin have very mild effect on the overall transcriptional changes (Nora et al., 2017).”
The role of transcription in shaping the spatial organization of the genome
van Steensel, B., & Furlong, E. E. M. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0114-6 · Cited by 247
Systematic evaluation of chromosome conformation capture assays
Oksuz, B. A., Yang, L., Abraham, S., Venev, S. V., Krietenstein, N., Parsi, K. M., Özadam, H., Oomen, M. E., Nand, A., Mao, H. Z., et al. (2021) · Nature Methods · doi:10.1038/s41592-021-01248-7 · Cited by 249
“For NAtuRE MEtHODS | www.nature.com/naturemethods HeLa libraries we excluded the chromosomes with translocations and used only chromosomes 4, 14, 17, 18, 20 and 21.”
Self-citationX-Chromosome Inactivation: A Crossroads Between Chromosome Architecture and Gene Regulation
Galupa, R., & Heard, É. (2018) · Annual Review of Genetics · doi:10.1146/annurev-genet-120116-024611 · Cited by 257
Lamins Organize the Global Three-Dimensional Genome from the Nuclear Periphery
Zheng, X., Hu, J., Yue, S., Kristiani, L., Kim, M., Sauria, M. E. G., Taylor, J., Kim, Y., & Zheng, Y. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.05.017 · Cited by 250
Transcriptional Dysregulation of MYC Reveals Common Enhancer-Docking Mechanism
Schuijers, J., Manteiga, J. C., Weintraub, A. S., Day, D. S., Zamudio, A. V., Hnisz, D., Lee, T. I., & Young, R. A. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.056 · Cited by 232
“CTCF Enhancer-Docking Sites at Additional Genes Previous genomic studies have noted that CTCF might engender enhancer-promoter interactions at a minority of genes (Banani et al., 2017; Nora et al., 2017; Splinter et al., 2006; Zuin et al., 2014).”
BackgroundInfluentialTranscription shapes 3D chromatin organization by interacting with loop extrusion
Banigan, E. J., Tang, W., van den Berg, A. A., Stocsits, R. R., Wutz, G., Brandão, H. B., Busslinger, G. A., Peters, J., & Mirny, L. A. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2210480120 · Cited by 238
“However, while boundaries such as CTCF sites are stationary (Busslinger et al., 2017; Fudenberg et al., 2016; Nora et al., 2017; Sanborn et al., 2015; Wutz et al., 2017), RNAPs are mobile and can be dynamically controlled by transcriptional regulators.”
BackgroundSelf-citationTwo major mechanisms of chromosome organization
Mirny, L. A., Imakaev, M., & Abdennur, N. A. (2019) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2019.05.001 · Cited by 232
“Moreover, such affinity-based models cannot explain the experimentally observed fusion of neighboring TADs upon loss of CTCF or engineered deletion of CTCF sites [14,34,41,42].”
BackgroundMethodInfluentialSelf-citationPolymer physics predicts the effects of structural variants on chromatin architecture
Bianco, S., Lupiáñez, D. G., Chiariello, A. M., Annunziatella, C., Kraft, K., Schöpflin, R., Wittler, L., Andrey, G., Vingron, M., Pombo, A., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0098-8 · Cited by 215
Evaluating Enhancer Function and Transcription
Field, A. R., & Adelman, K. (2020) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-011420-095916 · Cited by 227
“Unlike compartment structure, however, TAD structure is largely invariant across cell types (76, 137), rendering these domains insufficient to explain the highly dynamic nature of enhancer activity in different cell states.”
BackgroundThree-dimensional chromatin landscapes in T cell acute lymphoblastic leukemia
Kloetgen, A., Thandapani, P., Ntziachristos, P., Ghebrechristos, Y. E., Nomikou, S., Lazaris, C., Chen, X., Hu, H., Bakogianni, S., Wang, J., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0602-9 · Cited by 219
Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome
Lu, J. Y., Chang, L., Li, T., Wang, T., Yin, Y., Zhan, G., Han, X., Zhang, K., Tao, Y., Percharde, M., et al. (2021) · Cell Research · doi:10.1038/s41422-020-00466-6 · Cited by 205
“S10b–i), which is consistent with the Hi-C results reported previously.(22,23,95)”
ResultCuartero, S., Weiss, F. D., Dharmalingam, G., Guo, Y., Ing-Simmons, E., Masella, S., Robles-Rebollo, I., Xiao, X., Wang, Y.-F., Barozzi, I., et al. (2018) · Nature Immunology · doi:10.1038/s41590-018-0184-1 · Cited by 210
CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention
Pugacheva, E. M., Kubo, N., Loukinov, D. I., Tajmul, M., Kang, S., Kovalchuk, A. L., Strunnikov, A. V., Zentner, G. E., Ren, B., & Lobanenkov, V. V. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1911708117 · Cited by 224
“These data are wholly consistent with the results from the previous studies using CTCF auxininducible degron system and with CTCF knockout mouse fibroblasts where, in the absence of CTCF, cohesin is no longer able to occupy CTCF binding sites (30, 31).”
ResultCoolpup.py: versatile pile-up analysis of Hi-C data
Flyamer, I. M., Illingworth, R. S., & Bickmore, W. A. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa073 · Cited by 220
Large-Scale Topological Changes Restrain Malignant Progression in Colorectal Cancer
Johnstone, S. E., Reyes, A., Qi, Y., Adriaens, C., Hegazi, E., Pelka, K., Chen, J. H., Zou, L.-L., Drier, Y., Hecht, V. C., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.030 · Cited by 189
Molecular basis of CTCF binding polarity in genome folding
Nora, E. P., Caccianini, L., Fudenberg, G., So, K., Kameswaran, V., Nagle, A., Uebersohn, A., Hajj, B., Saux, A. L., Coulon, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19283-x · Cited by 206
Self-citationCatarino, R. R., & Stark, A. (2018) · Genes & Development · doi:10.1101/gad.310367.117 · Cited by 215
“Indeed, depletion of CTCF or cohesin disrupts TADs and seems to instead favor contacts within active or respressive compartments (Hou et al. 2012; Seitan et al. 2013; Zuin et al. 2014; Ing-Simmons et al. 2015; Ulianov et al. 2016; Haarhuis et al. 2017; Nora et al. 2017; Rao et al. 2017; Schwarzer et al. 2017; Wutz et…”
BackgroundA chromosome folding intermediate at the condensin-to-cohesin transition during telophase
Abramo, K., Valton, A.-L., Venev, S. V., Özadam, H., Fox, A. N., & Dekker, J. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0406-2 · Cited by 202
“This temporal difference between TAD and loop formation, as compared to long-range inter-compartment interaction formation, might be related to the fact that these structures are formed by different mechanisms 14-16 .”
BackgroundMethodSelf-citationMcCord, R. P., Kaplan, N., & Giorgetti, L. (2020) · Molecular Cell · doi:10.1016/j.molcel.2019.12.021 · Cited by 220
“Global perturbations such as depletion of CTCF and cohesin have suggested that overall, the ‘significant’ structures associated to CTCF/cohesin are important for long range gene regulation of at least a subset of genes (Rao et al. 2017; Schwarzer et al. 2017; Nora et al. 2017).”
BackgroundMechanisms of Interplay between Transcription Factors and the 3D Genome
Kim, S., & Shendure, J. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.08.010 · Cited by 218
Myc Regulates Chromatin Decompaction and Nuclear Architecture during B Cell Activation
Kieffer-Kwon, K.-R., Nimura, K., Rao, S. S. P., Xu, J., Jung, S., Pękowska, A., Dose, M., Stevens, E., Mathé, E. A., Dong, P., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.07.013 · Cited by 210
“Furthermore, loops and loop domains vanish from the genome when CTCF is conditionally deleted (Nora et al., 2017).”
Landscape of cohesin-mediated chromatin loops in the human genome
Grubert, F., Srivas, R., Spacek, D. V., Kasowski, M. M., Ruiz-Velasco, M., Sinnott-Armstrong, N., Greenside, P., Narasimha, A. M., Liu, Q., Geller, B. S., et al. (2020) · Nature · doi:10.1038/s41586-020-2151-x · Cited by 203
Regulatory Landscaping: How Enhancer-Promoter Communication Is Sculpted in 3D
Robson, M. I., Ringel, A. R., & Mundlos, S. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.05.032 · Cited by 203
Regulation of single-cell genome organization into TADs and chromatin nanodomains
Szabo, Q., Donjon, A., Jerković, I., Papadopoulos, G. L., Cheutin, T., Bonev, B., Nora, E. P., Bruneau, B. G., Bantignies, F., & Cavalli, G. (2020) · Nature Genetics · doi:10.1038/s41588-020-00716-8 · Cited by 194
“5c), in agreement with the previously reported 2-to 3-fold decrease of CTCF level in untreated CTCF-AID compared to wild-type cells 11 .”
Self-citationAn efficient auxin-inducible degron system with low basal degradation in human cells
Li, S., Prasanna, X., Salo, V. T., Vattulainen, I., & Ikonen, E. (2019) · Nature Methods · doi:10.1038/s41592-019-0512-x · Cited by 191
CTCF is a DNA-tension-dependent barrier to cohesin-mediated loop extrusion
Davidson, I. F., Barth, R., Zaczek, M., van der Torre, J., Tang, W., Nagasaka, K., Janissen, R., Kerssemakers, J. W. J., Wutz, G., Dekker, C., et al. (2023) · Nature · doi:10.1038/s41586-023-05961-5 · Cited by 198
Enhancer selectivity in space and time: from enhancer–promoter interactions to promoter activation
Yang, J. H., & Hansen, A. S. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00710-6 · Cited by 191
Rodríguez-Carballo, E., Lopez‐Delisle, L., Zhan, Y., Fabre, P. J., Beccari, L. L., El-Idrissi, I., Huynh, T. H. N., Özadam, H., Dekker, J., & Duboule, D. (2017) · Genes & Development · doi:10.1101/gad.307769.117 · Cited by 180
“This may also explain why this boundary is still clearly detected in the almost complete absence of CTCF (data in (Nora et al. 2017)) Attracting landscapes, tolerated interactions and border directionality In several partial deletion alleles, ectopic interactions leaked over the border, leading to…”
BackgroundSelf-citationKey role for CTCF in establishing chromatin structure in human embryos
Chen, X., Ke, Y., Wu, K., Zhao, H., Sun, Y., Gao, L., Liu, Z., Zhang, J., Tao, W., Hou, Z., et al. (2019) · Nature · doi:10.1038/s41586-019-1812-0 · Cited by 190
Cohesin Disrupts Polycomb-Dependent Chromosome Interactions in Embryonic Stem Cells
Rhodes, J. D. P., Feldmann, A., Hernández-Rodríguez, B., Díaz, N., Brown, J. M., Fursova, N. A., Blackledge, N. P., Prathapan, P., Dobrinic, P., Huseyin, M. K., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2019.12.057 · Cited by 187
“Cohesin Counteracts Polycomb Chromatin Domain Interactions Independently of CTCF and Insulation (A) A schematic illustrating the genotype of the CTCF-AID-GFP cell line (Nora et al., 2017).”
BackgroundMethodInfluentialHuang, H., Zhu, Q., Jussila, A., Han, Y., Bintu, B., Kern, C., Conte, M., Zhang, Y., Bianco, S., Chiariello, A. M., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00863-6 · Cited by 187
Identifying cis Elements for Spatiotemporal Control of Mammalian DNA Replication
Sima, J., Chakraborty, A., Dileep, V., Michalski, M., Klein, K. N., Holcomb, N. P., Turner, J. L., Paulsen, M. T., Rivera‐Mulia, J. C., Trevilla‐García, C., et al. (2018) · Cell · doi:10.1016/j.cell.2018.11.036 · Cited by 188
“The Dppa2/4 domain corresponds to a TAD whose boundaries contain CTCF and cohesin binding sites (Nora et al., 2017; Yue et al., 2014; Dowen et al., 2014; Mumbach et al., 2016) and also align with compartment boundaries (Bonev et al., 2017).”
InfluentialSelf-citationHarnessing the Power of Proteolysis for Targeted Protein Inactivation
Verma, R., Mohl, D., & Deshaies, R. J. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.01.010 · Cited by 185
Preformed chromatin topology assists transcriptional robustness of Shh during limb development
Paliou, C., Guckelberger, P., Schöpflin, R., Heinrich, V., Esposito, A., Chiariello, A. M., Bianco, S., Annunziatella, C., Helmuth, J., Haas, S., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1900672116 · Cited by 163
“Finally, our data suggest that the modest transcriptional alterations upon global CTCF/Cohesin depletion in nondifferentiating cells can be crucial to the process of differentiation and morphogenesis (7, 8, 10).”
BackgroundESCO1 and CTCF enable formation of long chromatin loops by protecting cohesinSTAG1 from WAPL
Wutz, G., Ladurner, R., Hilaire, B. G. S., Stocsits, R. R., Nagasaka, K., Pignard, B., Sanborn, A. L., Tang, W., Várnai, C., Ivanov, M. P., et al. (2020) · eLife · doi:10.7554/elife.52091 · Cited by 173
“Consistent with previous results obtained by AID of CTCF (Nora et al., 2017; Wutz et al., 2017), depletion of CTCF by RNAi resulted in a reduction in the number of detectable loops (Figure 7A,C and D), and a decrease in the TAD insulation score (Figure 7E) but did not abolish long-range chromatin interactions.”
ResultDistinct roles of cohesin-SA1 and cohesin-SA2 in 3D chromosome organization
Kojic, A., Cuadrado, A., Koninck, M. D., Giménez-Llorente, D., Rodríguez-Corsino, M., Goméz-López, G., Dily, F. L., Martí-Renom, M. A., & Losada, A. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0070-4 · Cited by 183
“Recent studies depleting cohesin or CTCF in different cellular systems have led to the conclusion that TADs and compartments arise independently (21, 22).”
BackgroundResultThiecke, M. J., Wutz, G., Muhar, M., Tang, W., Bevan, S., Malysheva, V., Stocsits, R., Neumann, T., Zuber, J., Fraser, P., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107929 · Cited by 177
SMCHD1 Merges Chromosome Compartments and Assists Formation of Super-Structures on the Inactive X
Wang, C., Jégu, T., Chu, H.-P. C., Oh, H. J., & Lee, J. T. (2018) · Cell · doi:10.1016/j.cell.2018.05.007 · Cited by 170
Metadata
- Authors
- Nora, E. P., Goloborodko, A., Valton, A.-L., Gibcus, J. H., Uebersohn, A., Abdennur, N., Dekker, J., Mirny, L. A., & Bruneau, B. G.
- Affiliations
- Gladstone Institutes (US)
- Massachusetts Institute of Technology (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Nora, Elphège P.
- Bruneau, Benoit G.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 169
- Issue
- 5
- Pages
- 930-944.e22
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5538188
- OpenAlex
- W2614144400
- Semantic Scholar
- e8afa0f77d39684b99c6679f6d08fd74cf1d90f5
- Cited by
- 1,709
- References
- 100
- Citations by year
- 2026: 146 · 2025: 162 · 2024: 172 · 2023: 187 · 2022: 204 · 2021: 231 · 2020: 207 · 2019: 196 · 2018: 139 · 2017: 63
- FWCI
- 67.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- HAL (submittedVersion)
- Funders
- EMBO (ALTF523-2013)
- HSFP
- NIH/National Heart, Lung, and Blood Institute
- Bench to Bassinet Program (U01HL098179)
- Gladstone Institutes
- William H. Younger, Jr
- UCSF-Gladstone Institute of Virology & Immunology Center for AIDS Research (NIH P30 AI027763)
- National Human Genome Research Institute (R01 HG003143, U54 HG007010)
- NIH Common Fund (U54 DK107980, U01 DA 040588)
- 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 › Molecular Biology › Nuclear Structure and Function
- Keywords
- CTCF, topologically associating domains, chromatin insulation, chromosome folding, 3D genome organization, enhancer blocking, heterochromatin spreading, auxin-inducible degron, mouse embryonic stem cells, chromatin looping
- MeSH terms
- CCCTC-Binding Factor, Animals, Cell Cycle, Chromatin, Gene Expression Regulation, Indoleacetic Acids, Repressor Proteins, Transcription, Genetic, Chromosomes, Mammalian, Mice, Embryonic Stem Cells
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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