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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
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Items 601–700 of 1,001
Regulatory landscape of enhancer-mediated transcriptional activation
Kawasaki, K., & Fukaya, T. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2024.01.008 · Cited by 32
Sister chromatid cohesion halts DNA loop expansion
Bastié, N., Chapard, C., Cournac, A., Nejmi, S., Mboumba, H., Gadal, O., Thierry, A., Beckouët, F., & Koszul, R. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.02.004 · Cited by 27
TAD boundary deletion causes PITX2-related cardiac electrical and structural defects
Baudic, M., Murata, H., Bosada, F. M., Melo, U. S., Aizawa, T., Lindenbaum, P., van der Maarel, L. E., Guedon, A., Baron, E., Fremy, E., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-47739-x · Cited by 31
“In the mammalian genome, CTCF is dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs) 7 .”
Evolution and function of chromatin domains across the tree of life
Szalay, M.-F., Majchrzycka, B., Jerković, I., Cavalli, G., & Ibrahim, D. M. (2024) · Nature Structural & Molecular Biology · doi:10.1038/s41594-024-01427-y · Cited by 31
“…57 , and long-range contacts in plants might depend on two interaction modalities that could be similar in animals: on a general compartmentalization of active chromatin domains together through inter-domain looping and on more specific transcription factor-mediated chromatin interactions 133 .”
InfluentialAll eukaryotic SMC proteins induce a twist of −0.6 at each DNA loop extrusion step
Janissen, R., Barth, R., Davidson, I., Taschner, M., Gruber, S., Peters, J.-M., & Dekker, C. (2024) · bioRxiv · doi:10.1126/sciadv.adt1832 · Cited by 26
“DNA binding of CCCTC-binding factor (CTCF) demar-cates topologically associated domains (TADs) via an orientational interaction of CTCF with cohesin ( 29 , 57 – 63 ).”
Enhancer RNAs: Insights Into Their Biological Role
de Lara, J. C.-F., Arzate‐Mejía, R. G., & Targa, F. R. (2019) · Epigenetics Insights · doi:10.1177/2516865719846093 · Cited by 28
Alternative splicing signatures in preimplantation embryo development
Tian, G. G., Li, J., & Wu, J. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00399-y · Cited by 31
Single cell analysis pushes the boundaries of TAD formation and function
Luppino, J. M., & Joyce, E. F. (2020) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.03.005 · Cited by 29
“Importantly, these results are consistent with the widespread yet modest effect on gene expression observed following depletion of either cohesin or CTCF (Nora et al., 2017; Rao et al., 2017; Schwarzer et al., 2017; Wutz et al., 2017).”
BackgroundResultMany facades of CTCF unified by its coding for three-dimensional genome architecture
Wu, Q., Liu, P., & Wang, L. (2020) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2020.06.008 · Cited by 26
The transcriptional regulation of normal and malignant blood cell development
Edginton‐White, B., & Bonifer, C. (2021) · FEBS Journal · doi:10.1111/febs.15735 · Cited by 27
Liver-Specific Deletion of Mouse CTCF Leads to Hepatic Steatosis via Augmented PPARγ Signaling
Choi, Y., Song, M.-J., Jung, W.-J., Jeong, H., Park, S., Yang, B., Lee, E.-C., Joo, J.-S., Choi, D., Koo, S.-H., et al. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.07.016 · Cited by 23
Dimitrova, E., Feldmann, A., van der Weide, R. H., Flach, K. D., Lastuvkova, A., de Wit, E., & Klose, R. J. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00840-5 · Cited by 26
Contessoto, V. G., Dudchenko, O., Aiden, E. L., Wolynes, P. G., Onuchic, J. N., & Pierro, M. D. (2023) · Nature Communications · doi:10.1038/s41467-023-35909-2 · Cited by 27
Heterochromatin rewiring and domain disruption-mediated chromatin compaction during erythropoiesis
Li, D., Wu, F., Zhou, S., Huang, X., & Lee, H. (2023) · Nature Structural & Molecular Biology · doi:10.1038/s41594-023-00939-3 · Cited by 28
Quon, S., Yu, B., Russ, B. E., Tsyganov, K., Nguyen, H., Toma, C., Heeg, M., Hocker, J. D., Milner, J. J., Crotty, S., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.03.017 · Cited by 28
Nuclear genome organization in fungi: from gene folding to Rabl chromosomes
Torres, D. E., Reckard, A. T., Klocko, A. D., & Seidl, M. F. (2023) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuad021 · Cited by 29
Synergy between cis -regulatory elements can render cohesin dispensable for distal enhancer functionPreprint
Hansen, K. L., Adachi, A. S., Braccioli, L., Kadvani, S., Boileau, R. M., Pokorny, B., Shah, R., Anderson, E. C., Martinovic, M., Zhang, K., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.04.615095 · Cited by 28
Self-citationThree‐dimensional chromatin re‐organization during muscle stem cell aging
Yang, B. A., Larouche, J. A., Sabin, K., Fraczek, P. M., Parker, S. C. J., & Aguilar, C. A. (2023) · Aging Cell · doi:10.1111/acel.13789 · Cited by 27
Structure and dynamics of nuclear A/B compartments and subcompartments
Oji, A., Choubani, L., Miura, H., & Hiratani, I. (2024) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2024.102406 · Cited by 28
Members of an array of zinc-finger proteins specify distinct Hox chromatin boundaries
Ortabozkoyun, H., Huang, P., González-Buendía, E., Cho, H., Kim, S. Y., Tsirigos, A., Mazzoni, E. O., & Reinberg, D. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.08.007 · Cited by 28
“While intra-TAD activities in WT versus PATZ1 KO ESCs were similar, reduced intra-TAD activities were observed in PATZ1 KO MNs compared to WT (Figures S9C–”
Extrusion fountains are restricted by WAPL-dependent cohesin release and CTCF barriers
Liu, N. Q., Magnitov, M. D., Schijns, M. M. G. A., van Schaik, T., Teunissen, H., van Steensel, B., & de Wit, E. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf549 · Cited by 33
Xu, D., Ma, R., Zhang, J., Liu, Z., Wu, B., Peng, J., Zhai, Y., Gong, Q., Shi, Y., Wu, J., et al. (2018) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.8b01440 · Cited by 25
Navigating the crowd: visualizing coordination between genome dynamics, structure, and transcription
Shaban, H. A., Barth, R., & Bystricky, K. (2020) · Genome biology · doi:10.1186/s13059-020-02185-y · Cited by 28
“auxin-inducible degradation of the insulator protein CTCF, which acts together with cohesin in human cells to shape chromatin loop domains/TADs, has only a mild impact on transcriptional deregulation [171], and auxin-induced degradation of cohesin has a similarly modest effect on transcription [172].”
BackgroundSpatial Organization of Chromatin: Transcriptional Control of Adaptive Immune Cell Development
Pongubala, J. M. R., & Murre, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.633825 · Cited by 29
“The cis and trans physical contacts within these hubs may be established independently of CTCF/cohesin (68, 81, 118).”
BackgroundInfluentialDevenish, L. P., Mhlanga, M. M., & Negishi, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.662565 · Cited by 27
“Thus, an important discovery is that the action of Cohesin, and therefore the role of CTCF-loops, may be implicated in responses to stimuli and lineage commitment as opposed to gene expression at steady state.”
BackgroundInfluentialNon-Coding Variants in Cancer: Mechanistic Insights and Clinical Potential for Personalized Medicine
Lange, M., Begolli, R., & Giakountis, A. (2021) · Non-Coding RNA · doi:10.3390/ncrna7030047 · Cited by 26
CTCF DNA-binding domain undergoes dynamic and selective protein–protein interactions
Zhou, R., Tian, K., Huang, J. S., Duan, W., Fu, H., Feng, Y., Wang, H., Jiang, Y., Li, Y., Wang, R., et al. (2022) · iScience · doi:10.1016/j.isci.2022.105011 · Cited by 26
CTCF and cohesin promote focal detachment of DNA from the nuclear lamina
van Schaik, T., Liu, N. Q., Manzo, S. G., Peric‐Hupkes, D., de Wit, E., & van Steensel, B. (2022) · Genome biology · doi:10.1186/s13059-022-02754-3 · Cited by 29
“This result complements previous work indicating that CTCF loss does not trigger spreading of H3K27me3 heterochromatin [32].”
BackgroundMethodResultInfluential3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus
Zhao, M., Feng, D., Hu, L., Liu, L., Wu, J., Hu, Z. Q., Long, H., Kuang, Q., Ouyang, L., & Lu, Q. (2022) · Annals of the Rheumatic Diseases · doi:10.1136/ard-2022-222653 · Cited by 26
A gene subset requires CTCF bookmarking during the fast post‐mitotic reactivation of mouse ES cells
Chervova, A. A., Festuccia, N., Altamirano‐Pacheco, L., Dubois, A., & Navarro, P. (2022) · EMBO Reports · doi:10.15252/embr.202256075 · Cited by 27
“9.1 (Nora et al , 2017), both derived from mouse E14Tg2a strain 129/Ola – were cultured on standard serum and LIF conditions as previously described (Owens et al , 2019), passaged 1:10 every 2 – 3 days and regularly tested mycoplasma-free.”
InfluentialFunction and Evolution of the Loop Extrusion Machinery in Animals
Kabirova, E., Nurislamov, A. R., Shadskiy, A., Smirnov, A. V., Popov, A., Salnikov, P., Баттулин, Н. Р., & Fishman, V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24055017 · Cited by 27
Etiology of super-enhancer reprogramming and activation in cancer
Zhou, R. W., & Parsons, R. E. (2023) · Epigenetics & Chromatin · doi:10.1186/s13072-023-00502-w · Cited by 31
CTCF Expression is Essential for Somatic Cell Viability and Protection Against Cancer
Bailey, C. G., Metierre, C., Yue, F., Baidya, K., Filippova, G. N., Loukinov, D. I., Lobanenkov, V. V., Semaan, C., & Rasko, J. E. J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123832 · Cited by 25
“Acute depletion impacted on CTCF looping and insulation of TAD regions, but genomic compartmentalisation was maintained [50].”
del Fierro, A. T., den Hamer, B., Benetti, N., Jansz, N., Chen, K., Beck, T. J., Vanyai, H. K., Gurzau, A. D., Daxinger, L., Xue, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40992-6 · Cited by 26
Zhang, J., Donahue, G., Gilbert, M. B., Lapidot, T., Nicetto, D., & Zaret, K. S. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01547-z · Cited by 33
Genetic factors mediating long-range enhancer–promoter communication in mammalian development
Bower, G., & Kvon, E. Z. (2024) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2024.102282 · Cited by 30
“However, perhaps surprisingly, E-P loops and gene expression are largely maintained upon the acute loss of cohesin, CTCF, or YY1 [39,40,51–53 , 74].”
Large scale genomic reorganization of topological domains at the HoxD locus
Fabre, P. J., Leleu, M., Mormann, B. H., Lopez‐Delisle, L., Noordermeer, D., Beccari, L. L., & Duboule, D. (2017) · Genome biology · doi:10.1186/s13059-017-1278-z · Cited by 26
Matthews, B. J., & Waxman, D. J. (2020) · Epigenetics & Chromatin · doi:10.1186/s13072-020-00350-y · Cited by 22
Three-dimensional genome organization via triplex-forming RNAs
Farabella, I., Stefano, M. D., Soler-Vila, P., Marti-Marimon, M., & Martı́-Renom, M. A. (2021) · Nature Structural & Molecular Biology · doi:10.1038/s41594-021-00678-3 · Cited by 26
Nair, S. J., Suter, T., Wang, S. S., Lu, Y., Yang, F., & Rosenfeld, M. G. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.05.015 · Cited by 27
Kurotaki, D., Kikuchi, K., Cui, K., Kawase, W., Saeki, K., Fukumoto, J., Nishiyama, A., Nagamune, K., Zhao, K., Ozato, K., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2207009119 · Cited by 27
Liu, J., Zhu, S., Hu, W., Zhao, X., Shan, Q., Peng, W., & Xue, H. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20221288 · Cited by 26
“In Ctcf − / − T EFF cells, the loss of CTCF binding at the boundary anchors likely disrupted the integrity of the insulated neighborhoods (Nora et al., 2017), and hence exposing the incongruous sites to TFs other than CTCF.”
CEBPA Phase Separation Links Transcriptional Activity and 3D Chromatin Hubs
Christou‐Kent, M., Cuartero, S., Garcia‐Cabau, C., Rühle, J., Naderi, J., Erber, J., Neguembor, M. V., Plana-Carmona, M., Alcoverro-Bertran, M., de Andrés-Aguayo, L., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2023.112897 · Cited by 27
Diploid genome architecture revealed by multi-omic data of hybrid micePreprint
Han, Z., Cui, K., Placek, K., Hong, N., Lin, C., Chen, W., Zhao, K., & Jin, W. (2020) · Genome Research · doi:10.1101/gr.257568.119 · Cited by 26
“The TAD structure is relatively stable across different cell types, which requires the function of CTCF and cohesin (Dixon et al. 2012; Zuin et al. 2014; Nora et al. 2017; Ren et al. 2017; Wang et al. 2019).”
BackgroundCo-depletion of NIPBL and WAPL balance cohesin activity to correct gene misexpression
Luppino, J. M., Field, A. R., Nguyen, S. C., Park, D. S., Shah, P. P., Abdill, R. J., Lan, Y., Yunker, R., Jain, R., Adelman, K., et al. (2022) · PLoS Genetics · doi:10.1371/journal.pgen.1010528 · Cited by 34
SATB2 organizes the 3D genome architecture of cognition in cortical neurons
Wahl, N., Espeso‐Gil, S., Chietera, P., Nagel, A., Laighneach, A., Morris, D. W., Rajarajan, P., Akbarian, S., Dechant, G., & Apostolova, G. (2024) · Molecular Cell · doi:10.1016/j.molcel.2023.12.024 · Cited by 24
Narducci, D. N., & Hansen, A. S. (2025) · Molecular Cell · doi:10.1016/j.molcel.2024.11.032 · Cited by 25
Magnitov, M. D., Maresca, M., Saiz, N. A., Teunissen, H., Dong, J., Sathyan, K. M., Braccioli, L., Guertin, M. J., & de Wit, E. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.11.031 · Cited by 24
RETRACTED: Kinetic organization of the genome revealed by ultraresolution multiscale live imaging
Lee, J., Chen, L., Gaudin, S., Gupta, K., Novačić, A., Spakowitz, A. J., & Boettiger, A. N. (2025) · Science · doi:10.1126/science.adx2202 · Cited by 34
RetractedChoice of binding sites for CTCFL compared to CTCF is driven by chromatin and by sequence preference
Bergmaier, P., Weth, O., Dienstbach, S., Boettger, T., Galjart, N., Mernberger, M., Bartkuhn, M., & Renkawitz, R. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky483 · Cited by 25
“These expression changes are not dramatic as strong effects are only seen in a short and transient time window (42).”
BackgroundRodríguez-Carballo, E., Lopez‐Delisle, L., Yakushiji‐Kaminatsui, N., Ullate‐Agote, A., & Duboule, D. (2019) · BMC Biology · doi:10.1186/s12915-019-0677-x · Cited by 22
Chromatin and Nuclear Architecture: Shaping DNA Replication in 3D
Nathanailidou, P., Taraviras, S. L., & Lygerou, Z. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.07.003 · Cited by 28
Characterizing chromatin folding coordinate and landscape with deep learning
Xie, W. J., Qi, Y., & Zhang, B. (2020) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1008262 · Cited by 23
Dbx2 regulation in limbs suggests inter TAD sharing of enhancers
Beccari, L. L., Jaquier, G., Lopez‐Delisle, L., Rodríguez-Carballo, E., Mascrez, B., Gitto, S., Woltering, J. M., & Duboule, D. (2021) · Developmental Dynamics · doi:10.1002/dvdy.303 · Cited by 23
Building the genome architecture during the maternal to zygotic transition
Zhang, Y., & Xie, W. (2021) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2021.11.002 · Cited by 25
Li, F., Sun, H., Li, Y., Bai, X., Dong, X., Zhao, N., Meng, J., Sun, B., & Zhang, D. (2021) · BMC Cancer · doi:10.1186/s12885-021-09010-0 · Cited by 26
“Studies have shown that CTCF expression is involved in tumorigenesis [27] and can be used as a transcription factor to control gene expression by binding to the transcriptional initiation sites (TSSs) of many genes [28].”
BackgroundEctopic expression of meiotic cohesin generates chromosome instability in cancer cell line
Boukaba, A., Liu, J., Ward, C., Wu, Q., Arnaoutov, A., Liang, J., Pugacheva, E. M., Dasso, M., Lobanenkov, V. V., Esteban, M. A., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2204071119 · Cited by 24
“The sites of CTCF and cohesin cobinding (66, 95) contribute synergistically to the formation and maintenance of CTCF-anchored loops and TAD boundaries (85, 88).”
BackgroundAuxin-inducible degron 2 system deciphers functions of CTCF domains in transcriptional regulation
Hyle, J. W., Djekidel, M. N., Williams, J. S., Wright, S., Shao, Y., Xu, B.-S., & Li, C.-L. (2023) · Genome Biology · doi:10.1186/s13059-022-02843-3 · Cited by 19
“Overall, global nascent transcription changes following CTCF loss with the AID2 system were limited, which supported previous observations that CTCF loss minimally impacted global steady-state RNA expression [12, 18, 19].”
BackgroundMethodResultInfluentialA Kaleidoscope of Keratin Gene Expression and the Mosaic of Its Regulatory Mechanisms
Kalabusheva, E. P., Shtompel, A. S., Rippa, A. L., Ulianov, S. V., Razin, S. V., & Vorotelyak, E. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065603 · Cited by 26
A DNA tumor virus globally reprograms host 3D genome architecture to achieve immortal growth
Wang, C., Liu, X., Liang, J., Narita, Y., Ding, W.-Y., Li, D., Zhang, L., Wang, H.-B., Leong, M., Hou, I., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37347-6 · Cited by 20
Noh, M., Sim, J. Y., Kim, J., Ahn, J. H., Min, H., Lee, J.-U., Park, J.-S., Jeong, J. Y., Lee, J. Y., Lee, S. Y., et al. (2023) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2023.132932 · Cited by 28
Łaźniewski, M., Dawson, W., Rusek, A. M., & Plewczyński, D. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.08.003 · Cited by 24
“A more recent study involving a conditional degradation strategy in mouse embryonic stem cells suggests a far more profound change to chromatin structure upon a more complete CTCF depletion [87].”
BackgroundCompetition Between Transcription and Loop Extrusion Modulates Promoter and Enhancer DynamicsPreprint
Platania, A., Erb, C., Barbieri, M., Molcrette, B., Grandgirard, E., de Kort, M. A. C., Meaburn, K. J., Taylor, T., Shchuka, V. M., Kocanova, S., et al. (2023) · SSRN Electronic Journal · doi:10.1101/2023.04.25.538222 · Cited by 32
3D Chromosomal Landscapes in Hematopoiesis and Immunity
Kloetgen, A., Thandapani, P., Tsirigos, A., & Aifantis, I. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.07.003 · Cited by 25
Polycomb proteins as organizers of 3D genome architecture in embryonic stem cells
Pachano, T., Crispatzu, G., & Rada-Iglesias, Á. (2019) · Briefings in Functional Genomics · doi:10.1093/bfgp/elz022 · Cited by 25
3D Genome Organization as an Epigenetic Determinant of Transcription Regulation in T Cells
Papadogkonas, G., Papamatheakis, D.-A., & Spilianakis, C. G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.921375 · Cited by 25
Postmitotic differentiation of human monocytes requires cohesin-structured chromatin
Minderjahn, J., Fischer, A. H., Maier, K., Mendes, K., Nuetzel, M., Raithel, J., Stanewsky, H., Ackermann, U., Månsson, R., Gebhard, C., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31892-2 · Cited by 24
Chi, Y., Shi, J., Xing, D., & Tan, L. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.959688 · Cited by 25
“, 2014); however, evidence both for and against this proposed function has accumulated (Nora et al., 2017; Rao et al., 2017; Ghavi-Helm et al., 2019; Zuin et al., 2022).”
BackgroundBroad Chromatin Domains: An Important Facet of Genome Regulation
Carelli, F. N., Sharma, G., & Ahringer, J. (2017) · BioEssays · doi:10.1002/bies.201700124 · Cited by 24
A tour of 3D genome with a focus on CTCF
Wang, D. C., Wang, W. Y., Zhang, L., & Wang, X. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.07.020 · Cited by 25
Zhang, Y., Hyle, J. W., Wright, S., Shao, Y., Zhao, X., Zhang, H., & Li, C. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1909720116 · Cited by 24
Kurup, J. T., Han, Z., Jin, W., & Kidder, B. L. (2020) · Development · doi:10.1242/dev.188516 · Cited by 23
Galupa, R., Picard, C., Servant, N., Nora, E. P., Zhan, Y., van Bemmel, J. G., Marjou, F. E., Johanneau, C., Borensztein, M., Ancelin, K., et al. (2022) · Development · doi:10.1242/dev.200568 · Cited by 23
Self-citationZhu, Y., Lee, H., White, S. M., Weimer, A. K. K., Monte, E., Horning, A. M., Nevins, S. A., Esplin, E. D., Paul, K., Krieger, G., et al. (2024) · Nature Cancer · doi:10.1038/s43018-024-00823-z · Cited by 24
“E interaction and gene expression 12,13,22,23 .”
Long-range enhancer-controlled genes are hypersensitive to regulatory factor perturbations
Tjalsma, S. J. D., Rinzema, N. J., Verstegen, M. J. A. M., Robers, M. J., Nieto-Aliseda, A., Gremmen, R., Allahyar, A., Muraro, M. J., Krijger, P. H. L., & de Laat, W. L. (2025) · Cell Genomics · doi:10.1016/j.xgen.2025.100778 · Cited by 30
Mujahed, H., Miliara, S., Neddermeyer, A., Bengtzén, S., Nilsson, C. C., Deneberg, S., Cordeddu, L., Ekwall, K., Lennartsson, A., & Lehmann, S. (2020) · Blood · doi:10.1182/blood.2019002326 · Cited by 24
Kyrchanova, O., Klimenko, N. S., Postika, N., Bonchuk, A. N., Zolotarev, N., Maksimenko, O. G., & Georgiev, P. G. (2021) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2021.194733 · Cited by 24
Zhu, X., Qi, C.-Y., Wang, R.-Y., Lee, J.-H., Shao, J., Bei, L.-X., Xiong, F., Nguyen, P. T., Li, G., Krakowiak, J., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111576 · Cited by 20
“The cutoff of different categories of compartment shifts (in Figure S6C TADs and insulation scores and directionality index—”
InfluentialLive-cell imaging of chromatin contacts opens a new window into chromatin dynamics
van Staalduinen, J., van Staveren, T., Grosveld, F. G., & Wendt, K. S. (2023) · Epigenetics & Chromatin · doi:10.1186/s13072-023-00503-9 · Cited by 26
TULIPs decorate the three-dimensional genome of PFA ependymoma
Johnston, M. J. G., Lee, J. J. Y., Hu, B., Nikolić, A., Hasheminasabgorji, E., Baguette, A., Paik, S., Chen, H., Kumar, S. A., Chen, C. C. L., et al. (2024) · Cell · doi:10.1016/j.cell.2024.06.023 · Cited by 22
“Similarly, 72.6% of PFA-enriched anchors overlap CTCF sites (OR 3.69, 95% confidence interval: 2.58–5.37) (Figure 2G).”
BackgroundInfluentialRemodeling of Il4-Il13-Il5 locus underlies selective gene expression
Nagashima, H., Shayne, J., Jiang, K., Petermann, F., Pękowska, A., Kanno, Y., & O’Shea, J. J. (2024) · Nature Immunology · doi:10.1038/s41590-024-02007-4 · Cited by 23
“After a cell is committed to a cell state, the 3D chromatin regulated by cohesin has been reported to not play a major role for proper gene expression 44,45 .”
Nagai, L. A. E., Park, S., & Nakai, K. (2019) · BMC Medical Genomics · doi:10.1186/s12920-018-0437-8 · Cited by 22
“We observed CTCF motifs enriched only at TAD boundaries in ES cells, which is consistent with a previous report [44].”
ResultHi-C detects novel structural variants in HL-60 and HL-60/S4 cell lines
Jacobson, E. C., Grand, R. S., Perry, J. K., Vickers, M. H., Olins, A. L., Olins, D. E., & O'Sullivan, J. M. (2019) · Genomics · doi:10.1016/j.ygeno.2019.05.009 · Cited by 23
The interplay between asymmetric and symmetric DNA loop extrusion
Banigan, E., & Mirny, L. (2020) · bioRxiv · doi:10.7554/elife.63528 · Cited by 19
“…topologically associated domain (TAD) formation in interphase (Banigan et al., 2020), where extrusion by the SMC complex cohesin can be paused by barriers such as CTCF (Sanborn et al., 2015; de Wit et al., 2015; Fudenberg et al., 2016; Busslinger et al., 2017; Nora et al., 2017; Wutz et al., 2017).”
BackgroundSelf-citationChakraborty, S., Wenzlitschke, N., Anderson, M. J., Eraso, A., Baudic, M., Thompson, J. J., Evans, A. A., Shatford-Adams, L. M., Chari, R., Awasthi, P., et al. (2025) · Developmental Cell · doi:10.1016/j.devcel.2025.02.002 · Cited by 22
Tiana, G., & Giorgetti, L. (2017) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2017.10.016 · Cited by 19
Models of polymer physics for the architecture of the cell nucleus
Esposito, A., Annunziatella, C., Bianco, S., Chiariello, A. M., Fiorillo, L., & Nicodemi, M. (2018) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1444 · Cited by 20
“genomic distance-related decay; however, it is uniform with no patterns whatsoever, hence the FG cannot explain the formation of specific DNA loops, as well as TADs and the other mentioned patterns observed in more recent experimental data (Dixon et al., 2012; Nora et al., 2017; Rao et al., 2017).”
ResultZhou, Q., Sheng, C., Zheng, S., Wang, Z., Guan, P., Zhu, Z., Huang, X., Zhou, C., & Li, G. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac893 · Cited by 22
Marina-Zárate, E., Rodríguez-Ronchel, A., Gómez, M. J., Sánchez‐Cabo, F., & Ramiro, A. R. (2023) · iScience · doi:10.1016/j.isci.2023.106106 · Cited by 22
“Higher affinity CBSs are enriched in TAD boundaries and long-range interactions, suggesting that high-affinity CBSs play an important role in constitutive chromatin architecture.(9,22,25,26) However, no relationship has been established between CBS affinity and other specific CTCF functions, such as the promotion of 1…”
BackgroundResultYang, B., Kim, S., Jung, W.-J., Kim, K., Kim, S., Kim, Y.-J., Kim, T., Lee, E.-C., Joo, J.-S., Park, C. G., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36948-5 · Cited by 23
Nakato, R., Sakata, T., Wang, J., Nagai, L. A. E., Nagaoka, Y., Oba, G. M., Bando, M., & Shirahige, K. (2023) · Nature Communications · doi:10.1038/s41467-023-41316-4 · Cited by 22
“Asreported in previous studies 17,19 , broad histone marks (H3K36me3, H3K27me3, andH3K9me3)werenotsubstantiallyaffected,suggestingthattheloss of TAD boundaries does not cause these histone modi fi cations to spread.”
InfluentialImpact of CAR Agonist Ligand TCPOBOP on Mouse Liver Chromatin Accessibility
Lodato, N. J., Rampersaud, A., & Waxman, D. J. (2018) · Toxicological Sciences · doi:10.1093/toxsci/kfy070 · Cited by 19
“, 2016) and thereby enable linearly distant chromosomal regions to interact within the large TAD-based DNA loops that segment each chromosome (Faure et al., 2012; Nora et al., 2017; Rao et al., 2014).”
BackgroundDefining the Transcriptional Ecosystem
Silveira, M. A. D., & Bilodeau, S. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.11.022 · Cited by 22
Zhang, X., Wang, Y., Chiang, H.-C., Hsieh, Y.-P., Lu, C., Park, B. H., Jatoi, I., Jin, V. X., Hu, Y., & Li, R. (2019) · Breast Cancer Research · doi:10.1186/s13058-019-1132-1 · Cited by 22
“Targeted degradation of CTCF leads to disruption of chromatin loops [89].”
BackgroundCamlin, N. J., & Evans, J. P. (2019) · Biology of Reproduction · doi:10.1093/biolre/ioz113 · Cited by 21
Ghavi-Helm, Y. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.09.010 · Cited by 20
3D genome organization during lymphocyte development and activation
Schoonhoven, A. O.-V., Huylebroeck, D., Hendriks, R. W., & Stadhouders, R. (2019) · Briefings in Functional Genomics · doi:10.1093/bfgp/elz030 · Cited by 24
Zhao, H., Li, Z., Zhu, Y., Bian, S., Zhang, Y., Qin, L., Naik, A. K., He, J., Zhang, Z., Krangel, M. S., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa711 · Cited by 21
“Several studies reported that cohesin, CTCF, or WAPL depletion or CTCF binding loss mainly affect the expression of the genes near TAD boundaries or CTCF binding sites (18,27,41–42).”
Saha, P., Sowpati, D. T., Soujanya, M., Srivastava, I., & Mishra, R. K. (2020) · Epigenetics & Chromatin · doi:10.1186/s13072-020-00358-4 · Cited by 22
“Several recent reports have suggested variable effects of disruption of genome organization on gene expression, for example, the drastic phenotypic effect of CTCF depletion to mild changes in gene expression upon acute CTCF depletion in cultured cells (Nora et al. 2017)(Kubo et al.”
BackgroundBAZ2A safeguards genome architecture of ground‐state pluripotent stem cells
Dalcher, D., Tan, J. Y., Bersaglieri, C., Peña‐Hernández, R., Vollenweider, E., Zeyen, S., Schmid, M. W., Bianchi, V., Butz, S., Roganowicz, M., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2020105606 · Cited by 21
“Removal or depletion of chromatin-associated cohesin eliminates all loop domains and increased compartmentalization (Haarhuis et al , 2017; Nora et al , 2017; Rao et al , 2017; Schwarzer et al , 2017).”
Influential
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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