The DOI matches its Crossref record; 102 of the 102 references it cites were found in a registry or an index; none of the 21 sources its claims cite is checked for support yet.
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.
Overview
AI snapshot
Written from the paper’s full text.
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.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 21 cited sources checked · 0 supported · 0 flagged
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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Disruption of Local Insulation Does Not Affect Higher-Order Chromosome Folding · hedged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § CTCF Binding Is Not a Direct Impediment to H3K27me3 Spreading in mESCs · 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
“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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
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.
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
“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
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
“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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
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.
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
“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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
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.
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
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Gene targeting · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We 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
Strength:hedged· 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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We 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
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.
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We 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
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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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 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
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
“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
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Strength:hedged· 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
“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
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
“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
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.
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 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
Cited by
Sorted by citations
Items 901–1,000 of 1,001
Capturing 3D Chromatin Maps of Human Primary Monocytes: Insights From High-Resolution Hi-C
Xia, Y., Liu, X., Mu, W., Ma, C., Wang, L., Jiao, Y., Cui, B., Hu, S., Gao, Y., Liu, T., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.837336 · Cited by 12
Li, Y., Boadu, F., Highsmith, M. R., Hagen, D. E., Cheng, J. J., & Rivera, R. M. (2022) · iScience · doi:10.1016/j.isci.2022.104269 · Cited by 12
Making connections: enhancers in cellular differentiation
Herrmann, J. C., Beagrie, R. A., & Hughes, J. R. (2021) · Trends in Genetics · doi:10.1016/j.tig.2021.10.008 · Cited by 14
The Interplay of Transcription and Genome Topology Programs T Cell Development and Differentiation
Zhao, X., Zhu, S., Peng, W., & Xue, H. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2200625 · Cited by 14
One ring to bind them – Cohesin’s interaction with chromatin fibers
Gines, M. M., van Staveren, T., & Wendt, K. S. (2019) · Essays in Biochemistry · doi:10.1042/ebc20180064 · Cited by 14
Marshall, A. E., Ishak, C. A., & Dick, F. A. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00452-19 · Cited by 13
Architectural proteins for the formation and maintenance of the 3D genome
Li, M., Gan, J., Sun, Y., Xu, Z., Yang, J., Sun, Y., & Li, C. (2020) · Science China Life Sciences · doi:10.1007/s11427-019-1613-3 · Cited by 15
“depletion, most loop domains disappeared while high-order genomic compartments were largely preserved (Nora et al., 2017), suggesting that CTCF is necessary for TAD insulation and loop formation.”
BackgroundInfluentialAdaptation of the AID system for stem cell and transgenic mouse research
Pryzhkova, M. V., Xu, M. J., & Jordan, P. W. (2020) · Stem Cell Research · doi:10.1016/j.scr.2020.102078 · Cited by 12
“However, limited applications have been reported in ESCs (Baker et al., 2016; Brosh et al., 2016; Friman et al., 2019; Nora et al., 2017; Owens et al., 2019; Sybirna et al., 2020).”
BackgroundInfluentialLuo, Z., Hu, T., Jiang, H., Wang, R., Xu, Q., Zhang, S. V., Cao, J., & Song, X. (2020) · Genome Research · doi:10.1101/gr.241687.118 · Cited by 17
“2014), and TADs are almost lost after depletion of CTCF in mammalian cells (Nora et al. 2017).”
BackgroundHuang, H., Zhu, Q.-S., Jussila, A. P., Han, Y., Bintu, B., Kern, C., Conte, M., Zhang, Y.-X., Bianco, S., Chiariello, A., et al. (2020) · bioRxiv · doi:10.1101/2020.07.07.192526 · Cited by 14
DNA methylation insulates genic regions from CTCF loops near nuclear specklesPreprint
Roseman, S. A., Siegenfeld, A. P., Lee, C., Lue, N. Z., Waterbury, A. L., & Liau, B. B. (2024) · eLife · doi:10.7554/elife.102930 · Cited by 15
“The architectural protein CTCF establishes the anchors of many DNA loops and TADs likely by blocking loop extrusion by cohesin ( Nora et al., 2017 ; Wendt et al., 2008 ; Li et al., 2020 ; Fudenberg et al., 2016 ; Kim et al., 2019 ; Davidson et al., 2019 ; Xiang and Corces, 2021 ; Hansen et al.,…”
InfluentialErythropoietin Regulates Transcription and YY1 Dynamics in a Pre-Established Chromatin Architecture
Perreault, A. A., Brown, J. D., & Venters, B. J. (2020) · iScience · doi:10.1016/j.isci.2020.101583 · Cited by 13
Tsujikawa, L. M., Kharenko, O. A., Stotz, S. C., Rakai, B. D., Sarsons, C. D., Gilham, D., Wasiak, S., Fu, L., Sweeney, M., Johansson, J. O., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113230 · Cited by 13
Smits, W. K., Vermeulen, C., Hagelaar, R., Kimura, S., Vroegindeweij, E. M., Buijs-Gladdines, J. G. C. A. M., van de Geer, E., Verstegen, M. J. A. M., Splinter, E., van Reijmersdal, S. V., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112373 · Cited by 13
Reprogramming of three-dimensional chromatin organization in the early embryo
Theis, A., & Harrison, M. M. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102613 · Cited by 12
Shifting landscapes: the role of 3D genomic organizations in gene regulatory strategies
Hehmeyer, J., Spitz, F., & Marlow, H. Q. (2023) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2023.102064 · Cited by 11
Quantifying dynamic pro-inflammatory gene expression and heterogeneity in single macrophage cells
Naigles, B., Narla, A. V., Soroczynski, J., Tsimring, L. S., & Hao, N. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105230 · Cited by 11
“A fl exible linker sequence (amino acid sequence GDGAGLIN) was used between IRF1 and the SYFP2 tag, and a T2A sequence was used between the protein and fl uorescent tag for CXCL10 and CXCL9 (70).”
BackgroundMethodInfluentialDNA replication and replication stress response in the context of nuclear architecture
González‐Acosta, D., & Lopes, M. (2023) · Chromosoma · doi:10.1007/s00412-023-00813-7 · Cited by 12
“…imaging experiments show that the MCM complex is a physical barrier for loop extruding cohesin (Dequeker et al. 2022), as previously shown for converging CTCF binding sites (Gassler et al. 2017; Nora et al. 2017; Wutz et al. 2017) and transcription (Jeppsson et al. 2022; Banigan et al. 2023).”
BackgroundPHF2 regulates genome topology and DNA replication in neural stem cells via cohesin
Feng, J., Chuah, Y. H., Liang, Y., Cipta, N. O., Zeng, Y., Warrier, T., Elfar, G. A., Yoon, J., Grinchuk, O. V., Tay, E. X. Y., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae457 · Cited by 12
“Indeed, CTCF or cohesin loss eliminates TADs and well-demarcated loops in Hi-C analysis, indicating their key role in TAD formation and maintenance ( 8–10 ).”
Vats, A., & Laimins, L. A. (2025) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00153-23 · Cited by 12
“Cellular chromatin is arranged in DNA loops, and these topological-associated domains (TADS) are frequently anchored through the binding of complexes consisting of the insulator, CTCF, the cohesion, SMC1, and TOP2β (119).”
CTCF/RAD21 organize the ground state of chromatin–nuclear speckle association
Yu, R., Roseman, S. A., Siegenfeld, A. P., Gardner, Z., Nguyen, S. C., Tran, K. A., Joyce, E. F., Jain, R., Liau, B. B., Krantz, I. D., et al. (2025) · Nature Structural & Molecular Biology · doi:10.1038/s41594-024-01465-6 · Cited by 22
Two CTCF motifs impede cohesin-mediated DNA loop extrusion
Barth, R., Janissen, R., Muras, L., van der Torre, J., Litos, G., van der Sluis, E. O., van den Berg, A., Davidson, I. F., Peters, J., & Dekker, C. (2025) · Molecular Cell · doi:10.1016/j.molcel.2025.11.001 · Cited by 14
Nuclear organization mediates cancer-compromised genetic and epigenetic control
Zaidi, S. K., Fritz, A. J., Tracy, K. M., Gordon, J. A. R., Tye, C. E., Boyd, J. R., van Wijnen, A. J., Nickerson, J. A., Imbalzano, A. N., Lian, J. B., et al. (2018) · Advances in Biological Regulation · doi:10.1016/j.jbior.2018.05.001 · Cited by 12
“Studies in the past few years have characterized intra- and inter-chromosomal interactions that impact gene activation and repression (Barutcu et al., 2015, 2016a, 2016b, 2017; Dekker and Mirny, 2016; Fritz et al., 2016, 2017; Gibcus and Dekker, 2013; Hnisz et al., 2016; Hou and Corces, 2012; Naumova et al., 2013; Nor…”
BackgroundTrait-associated noncoding variant regions affect TBX3 regulation and cardiac conduction
van Weerd, J. H., Mohan, R. A., van Duijvenboden, K., Hooijkaas, I. B., Wakker, V., Boukens, B. J., Barnett, P., & Christoffels, V. M. (2020) · eLife · doi:10.7554/elife.56697 · Cited by 12
Predictive Polymer Models for 3D Chromosome Organization
Chiang, M., Forte, G., Gilbert, N., Marenduzzo, D., & Brackley, C. A. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-1390-0_14 · Cited by 16
Bellefroid, M., Rodari, A., Galais, M., Krijger, P. H. L., Tjalsma, S. J. D., Nestola, L., Plant, E., Vos, E. S. M., Cristinelli, S., Driessche, B. V., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac107 · Cited by 12
TFIIIC-based chromatin insulators through eukaryotic evolution
Sizer, R. E., Chahid, N., Butterfield, S. P., Donze, D., Bryant, N. J., & White, R. J. (2022) · Gene · doi:10.1016/j.gene.2022.146533 · Cited by 10
Costea, J., Schoeberl, U. E., Malzl, D., von der Linde, M., Fitz, J., Gupta, A., Makharova, M., Goloborodko, A. A., & Pavri, R. (2022) · Molecular Cell · doi:10.1016/j.molcel.2023.01.014 · Cited by 12
Self-citationFeng, C., Wang, J., & Chu, X. (2023) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjad042 · Cited by 12
“…an important factor in gene regulation during the cell-state transition, emerging evidence shows that modulations of chromosome structure, e.g. disruption of TAD boundaries ( Nora et al., 2017 ; Ghavi-Helm et al., 2019 ; Stik et al., 2020 ) , have little impact on the acquisition of new cell fates.”
BackgroundMassively parallel characterization of insulator activity across the genome
Hong, C. K., Wu, Y., Erickson, A., Li, J., Federico, A. J., & Cohen, B. A. (2024) · Nature Communications · doi:10.1038/s41467-024-52599-6 · Cited by 12
“We apply MPIRE to assay three insulator sequences at thousands of genomic locations and fi nd that each insulator functions in locations with distinguishable properties.”
BackgroundMethodCTCF supports preferentially short lamina-associated domains
Kaczmarczyk, L. S., Levi, N., Segal, T., Salmon‐Divon, M., & Gerlitz, G. (2022) · Chromosome Research · doi:10.1007/s10577-022-09686-5 · Cited by 12
Epigenetics, Enhancer Function and 3D Chromatin Organization in Reprogramming to Pluripotency
Hörnblad, A., & Remeseiro, S. (2022) · Cells · doi:10.3390/cells11091404 · Cited by 14
Three‐dimensional genome architecture in health and disease
Ouimette, J., Rougeulle, C., & Veitia, R. A. (2018) · Clinical Genetics · doi:10.1111/cge.13219 · Cited by 15
“A recent study has shown that depletion of CTCF leads to loss of most TAD boundaries and to the appearance of inter-TAD interactions.(51) Another important feature of CTCF is its association with the nuclear matrix, thought to be involved in the formation of laminaassociated domains, another defining component of geno…”
BackgroundModeling three-dimensional genomic organization in evolution and pathogenesis
Diament, A., & Tuller, T. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.07.008 · Cited by 11
Baudement, M.-O., Cournac, A., Court, F., Seveno, M., Parrinello, H., Reynès, C., Sabatier, R., Bouschet, T., Yi, Z., Sallis, S., et al. (2018) · Genome Research · doi:10.1101/gr.237073.118 · Cited by 13
RNA interactions with CTCF are essential for its proper functionPreprint
Saldaña-Meyer, R., Rodriguez-Hernaez, J., Nishana, M., Jácome-López, K., Nora, E. P., Bruneau, B. G., Furlan-Magaril, M., Skok, J. A., & Reinberg, D. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/530014 · Cited by 12
“The depletion of either factor has drastic effects on chromatin structure wherein TADs essentially disappear (Nora et al., 2017; Rao et al., 2017).”
BackgroundMethodResultInfluentialSelf-citationDefining the relative and combined contribution of CTCF and CTCFL to genomic regulationPreprint
Nishana, M., Ha, C. J., Rodriguez-Hernaez, J., Ranjbaran, A., Chio, E., Nora, E. P., Badri, S., Kloetgen, A., Bruneau, B. G., Tsirigos, A., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2019.12.14.874560 · Cited by 12
Self-citationCTCF is a DNA-tension-dependent barrier to cohesin-mediated DNA loop extrusionPreprint
Davidson, I., Barth, R., Zaczek, M., van der Torre, J., Tang, W., Nagasaka, K., Janissen, R., Kerssemakers, J., Wutz, G., Dekker, C., et al. (2022) · bioRxiv · doi:10.1101/2022.09.08.507093 · Cited by 3
Chromatin insulators in gene regulation and 3D genome organization
Sultana, H., Kunar, R., & Matera, A. G. (2025) · Biochemical Society Transactions · doi:10.1042/bst20253036 · Cited by 11
“Loss of CTCF resulted in loss of borders at TADs, but overall compaction was not affected by the loss of CTCF, but the loss of cohesin resulted in an overall loss of compaction [42,58].”
InfluentialDeciphering the regulatory landscape of enhancer RNAs in health and disease
Wang, Q., ten Dijke, P., & Fan, C. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02436-z · Cited by 15
De novo formation of cis-regulatory contacts in the absence of NIPBL-driven chromatin loop extrusion
Aboreden, N. G., Zhao, H., Yang, J., Shan, F., Liu, F., Hansen, A. S., Zhang, H., & Blobel, G. A. (2026) · Nature Genetics · doi:10.1038/s41588-026-02565-3 · Cited by 21
PDS5 proteins control genome architecture by limiting the lifetime of cohesin-NIPBL complexes
Wutz, G., Davidson, I. F., Banigan, E. J., Stocsits, R. R., Kawasumi, R., Tang, W., Nagasaka, K., Costantino, L., Jansen, R., Hirota, K., et al. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.03.025 · Cited by 12
Self-citationTian, G. G., Zhao, X., Hou, C., Xie, W., Li, X., Wang, Y., Wang, L., Li, H., Zhao, X., Li, J., et al. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04107-y · Cited by 10
3D genome alterations and editing in pathology
Tiukacheva, E. A., Ulianov, S. V., Karpukhina, A. A., Razin, S. V., & Vassetzky, Y. S. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.02.005 · Cited by 14
Interplay between epigenome and 3D chromatin structure
Han, M.-H., Issagulova, D., & Park, M. (2023) · BMB Reports · doi:10.5483/bmbrep.2023-0197 · Cited by 13
“Importantly, loop extrusion and compartmentalization operate through distinct mechanisms, and perturbing one may influence, though not necessarily abolish, the other (29-33).”
BackgroundLi, S., Wang, Y., van der Stoel, M. M., Zhou, X., Madhusudan, S., Kanerva, K., Nguyen, V. D., Eskici, N., Olkkonen, V. M., Zhou, Y., et al. (2024) · Genome biology · doi:10.1186/s13059-024-03187-w · Cited by 11
Stepwise de novo establishment of inactive X chromosome architecture in early development
Du, Z., Hu, L., Zou, Z., Liu, M., Li, Z., Lu, X., Harris, C. E., Xiang, Y., Chen, F., Yu, G., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01897-2 · Cited by 12
“9c,d), consistent with previous work 45,46,52,72 .”
Active enhancers: recent research advances and insights into disease
Zhang, J., Wang, Q., Liu, J., Duan, Y., Liu, Z., Zhang, Z., & Li, C. (2024) · Biology Direct · doi:10.1186/s13062-024-00559-x · Cited by 18
“The boundaries of TADs in mammals are enriched in CTCF and cohesin binding [41, 42], and depletion of CTCF protein or cohesin leads to the disruption of TAD structures [43, 44].”
BackgroundChromatin-centric insights into DNA replication
Liu, Y., Zhangding, Z., Liu, X., & Hu, J. (2025) · Trends in Genetics · doi:10.1016/j.tig.2024.12.003 · Cited by 10
Qi, S., Shi, Z., & Yu, H. (2025) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2025.102310 · Cited by 13
Yang, X., Li, C., Ye, X., Zhang, J., Chen, X., Xu, J., Zhang, M., Feng, R., Hyle, J. W., Qi, W., et al. (2025) · Genome biology · doi:10.1186/s13059-025-03510-z · Cited by 11
Developing landscapes: genome architecture during early embryogenesis
van der Weide, R. H., & de Wit, E. (2019) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2019.04.009 · Cited by 10
Santana, J. F., Parida, M., Long, A., Wankum, J., Lilienthal, A. J., Nukala, K. M., & Manak, J. R. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.02.053 · Cited by 11
“…chromatin looping, and studies on CTCF and CP190 in vertebrates and invertebrates, respectively (Bushey et al., 2009; Matthews and Waxman, 2018; Nora et al., 2017; Pekowska et al., 2018; Rao et al., 2014), have proposed or confirmed a role for these insulator factors in tethering the chromatin…”
MEAF6 is essential for cell proliferation and plays a role in the assembly of KAT7 complexes
Matsuura, K., Tani, N., Usuki, S., Nishikawa‐Torikai, S., Okano, M., & Niwa, H. (2020) · Experimental Cell Research · doi:10.1016/j.yexcr.2020.112279 · Cited by 11
Epigenome rewiring in human pluripotent stem cells
Yan, J., & Huangfu, D. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.12.001 · Cited by 11
Regulation of the mitotic chromosome folding machines
Dekker, B., & Dekker, J. (2022) · Biochemical Journal · doi:10.1042/bcj20210140 · Cited by 11
Self-citationFluorescence-based super-resolution-microscopy strategies for chromatin studies
Burgers, T. C. Q., & Vlijm, R. (2023) · Chromosoma · doi:10.1007/s00412-023-00792-9 · Cited by 14
A novel auxin-inducible degron system for rapid, cell cycle-specific targeted proteolysis
Capece, M., Tessari, A., Mills, J., Vinciguerra, G. L. R., Louke, D. S., Lin, C., McElwain, B. K., Miles, W. O., Coppola, V., Davies, A. E., et al. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01191-4 · Cited by 11
“net/addgene:54234; RRID:Addgene_54234), while pEN435 pCAGGS-TagBFP-hGeminin-2A-mCherry-hCdt1-rbgpA-Frt-PGK-EM7-PuroRbpA-Frt Tigre targeting (Addgene #92139 [28]) was used as template for both hGeminin and hCdt1 tags.”
MethodChen, Y., Zhou, T., Liao, Z., Gao, W., Wu, J., Zhang, S., Li, Y., Liu, H., Zhou, H., Xu, C., et al. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01207-z · Cited by 11
“CTCF cooperates with the multi-subunit protein complex Cohesin to shape functional boundaries [17].”
BackgroundCTCF is essential for proper mitotic spindle structure and anaphase segregation
Chiu, K., Berrada, Y., Eskndir, N., Song, D., Fong, C., Naughton, S., Chen, T., Moy, S., Gyurmey, S., James, L., et al. (2023) · Chromosoma · doi:10.1242/prelights.34176 · Cited by 12
“Complete knockdown of CTCF was shown to be lethal (Moore et al. 2012; Nora et al. 2017; Wan et al. 2008), thus preventing the study of cell proliferation and mitosis.”
An evolutionary perspective of regulatory landscape dynamics in development and disease
Franke, M., & Gómez-Skármeta, J. L. (2018) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2018.06.009 · Cited by 11
Structural alteration of the nucleus for the reprogramming of gene expression
Tomikawa, J., & Miyamoto, K. (2021) · FEBS Journal · doi:10.1111/febs.15894 · Cited by 12
Wang, W., Ren, G., Hong, N., & Jin, W. (2019) · BMC Genomics · doi:10.1186/s12864-019-6379-5 · Cited by 11
Heterogeneity and Intrinsic Variation in Spatial Genome OrganizationPreprint
Finn, E. H., Pegoraro, G., Brandão, H. B., Valton, A.-L., Oomen, M. E., Dekker, J., Mirny, L. A., & Misteli, T. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/171801 · Cited by 14
“Hi-C libraries were generated from HFF cells cross-linked in 1% formaldehyde as described previously (15, 45, 46).”
MethodSelf-citationCompetent for commitment: you've got to have heart!Preprint
Jain, R., & Epstein, J. A. (2018) · Genes & Development · doi:10.1101/gad.308353.117 · Cited by 11
“Nora et al. (2017) used a clever inducible approach to reversibly degrade CTCF in murine ESCs to demonstrate that CTCF insulates a subset of TADs.”
MethodDynamic Control of Chromosome Topology and Gene Expression by a Chromatin ModificationPreprint
Bian, Q., Anderson, E. C., Brejc, K., & Meyer, B. J. (2017) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2017.82.034439 · Cited by 11
“Chromatin modification and three-dimensional (3D) chromosome structure play central roles in regulating gene expression (Vieux-Rochas et al. 2015; Dekker and Mirny 2016; Soshnev et al. 2016; Nora et al. 2017; Schuettengruber et al. 2017).”
CTCF looping is established during gastrulation in medaka embryosPreprint
Nakamura, R., Motai, Y., Kumagai, M., Nishiyama, H., Durand, N. C., Kondo, K., Kondo, T., Tsukahara, T., Shimada, A., Aiden, E. L., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/454082 · Cited by 11
Redundant and specific roles of cohesin STAG subunits in chromatin looping and transcription controlPreprint
Casà, V., Gines, M. M., Gusmao, E. G., Slotman, J. A., Zirkel, A., Josipović, N., Oole, E., van IJcken, W. F. J., Houtsmuller, A. B., Papantonis, A., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/642959 · Cited by 11
“Cohesin and CTCF form chromatin loops by tethering distant genomic regions (Hadjur et al. 2009; Nativio et al. 2009; Zuin et al. 2014a; Nora et al. 2017; Rao et al. 2017) preferentially between cohesin/CTCF sites with convergently orientated CTCF DNA motifs (Rao et al.”
BackgroundResultChapard, C., Meneu, L., Serizay, J., Westbrook, A., Routhier, E., Ruault, M., Bignaud, A., Thierry, A., Gourgues, G., Lartigue, C., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.21.520625 · Cited by 13
“4e ) and further suggest that loop extrusion can proceed through the Y/U chromatin junction to form a loop bridging the nearest cohesin enrichment sites on each side 35,36 .”
BackgroundStolper, R. J., Tsang, F. H., Georgiades, E., Hansen, L. L. P., Downes, D. J., Harrold, C. L., Hughes, J. R., Beagrie, R. A., Davies, B., Kassouf, M. T., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.07.556660 · Cited by 11
Dynamic chromatin organization and regulatory interactions in human endothelial cell differentiation
Alavattam, K. G., Mitzelfelt, K. A., Bonora, G., Fields, P., Yang, X., Chiu, H. S., Pabon, L., Bertero, A., Palpant, N. J., Noble, W. S., et al. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2022.11.003 · Cited by 10
“TADs and PPIs are similar in that both arise through a process of chromatin loop extrusion (Fudenberg et al., 2016; Nora et al., 2017; Sanborn et al., 2015).”
The material properties of mitotic chromosomes
Spicer, M. F. D., & Gerlich, D. W. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102617 · Cited by 10
Cis-Regulatory Elements in Mammals
Liu, X., Chen, M., Qu, X., Liu, W., Dou, Y., Liu, Q., Shi, D., Jiang, M., & Li, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010343 · Cited by 12
Wang, L., Chen, H., Zhuang, Y., Chen, K., Zhang, C., Cai, T., Yang, Q., Fu, H., Chen, X., Chitkineni, A., et al. (2024) · Plant Biotechnology Journal · doi:10.1111/pbi.14296 · Cited by 10
“…role in TAD establishment in animals through the formation of CTCF-cohesion complexes that stall TAD borders, a role that was supported both by experimentally editing CTCF motifs and by depleting these proteins (de Wit et al ., 2015; Guo et al ., 2015; Maass et al ., 2019; Nora et al ., 2017).”
BackgroundImage-based 3D genomics through chromatin tracing
Yang, T., & Wang, S. (2024) · Nature Reviews Methods Primers · doi:10.1038/s43586-024-00354-y · Cited by 10
“Previously known 3D genome regulators were discovered by perturbing one candidate gene at a time 92,93 .”
Interpreting the CTCF-mediated sequence grammar of genome folding with AkitaV2
Smaruj, P. N., Kamulegeya, F., Kelley, D. R., & Fudenberg, G. (2025) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1012824 · Cited by 9
“The global importance of CTCF and cohesin are evident by the loss of topologically associated domains (TADs) and dots (also termed loops) upon the depletion of either factor [3,4].”
BackgroundChromosomal domain formation by archaeal SMC, a roadblock protein, and DNA structure
(2025) · doi:10.1038/s41467-025-56197-y · Cited by 10
“The CTCF roadblock is the most studied example and can nicely explain the formation of multiple boundaries and boundary-associated Hi-C features such as stripes and boundary-to-boundary loops 10,16,17 .”
CREATE: cell-type-specific cis-regulatory element identification via discrete embedding
Cui, X., Yin, Q., Gao, Z., Li, Z., Chen, X., Lv, H., Chen, S., Liu, Q., Zeng, W., & Jiang, R. (2025) · Nature Communications · doi:10.1038/s41467-025-59780-5 · Cited by 10
“We took as insulators the CTCF 91,92 Chromatin immunoprecipitation sequencing (ChIP-seq) peaks for K562 and HepG2 cell types collected from the ENCODE project 93,94 .”
Cohesin prevents local mixing of condensed euchromatic domains in living human cells
Shimazoe, M. A., Iida, S., Minami, K., Higashi, K., Tamura, S., Kobayashi, Y., Fujishiro, S., Xiong, L., Nakazato, K., Ashwin, S. S., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02736-2 · Cited by 12
“Despite its role in TAD boundary formation 68 , CTCF loss did not affect nucleosome motion (Fig.”
Meiotic cohesin RAD21L shapes 3D genome structure and transcription in the male germline
Marín-Gual, L., Vara, C., Sainz-Urruela, R., Cuartero, Y., Álvarez-González, L., Felipe‐Medina, N., Garcia, F., Llano, E., Martı́-Renom, M. A., Pendás, A. M., et al. (2025) · Science Advances · doi:10.1126/sciadv.adv2283 · Cited by 10
“Acute cohesin deletion in somatic cell lines has been shown to have a minimal impact on gene expression ( 21 , 58 , 67 – 69 ).”
Ito, S., Das, N. D., Umehara, T., & Koseki, H. (2022) · Cancers · doi:10.3390/cancers14215404 · Cited by 13
A novel intergenic enhancer that regulates Bdnf expression in developing cortical neurons
Brookes, E., Cruz, B. M. D. L., Boulasiki, P., Au, H. Y. A., Varsally, W., Barrington, C., Hadjur, S., & Riccio, A. (2022) · iScience · doi:10.1016/j.isci.2022.105695 · Cited by 13
“CTCF (CCCTC-binding factor) and cohesin are key regulators of TAD boundaries, 45,46 and are known to bind to the Bdnf locus at promoter IV and intron 7 in mouse neurons.”
BackgroundGeneroso, S., Neguembor, M. V., Hershberg, E. A., Sadreyev, R. I., Kurimoto, K., Yabuta, Y., Ricci, R., Audergon, P. N. C. B., Bauer, M., Saitou, M., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2213810120 · Cited by 10
“Even while cohesin or CTCF depletion has only a modest impact on gene expression in the steady cell state (72, 82), another possibility is that cohesin could promote specific enhancer/promoter interactions switching silent genes to an active state during XCR.”
BackgroundGenome folding dynamics during the M-to-G1-phase transition
Zhang, H., & Blobel, G. A. (2023) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2023.102036 · Cited by 13
Crewe, M., Segev, A., Rueda, R., & Madabhushi, R. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03762-5 · Cited by 9
“Acute degradation of CTCF results in genome-wide loss of CTCF-anchored loops and TAD insulation, suggesting that CTCF plays a crucial role in chromosome organization [8, 9].”
Location, location, location: nuclear structure regulates gene expression in neurons
Brookes, E., & Riccio, A. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.03.009 · Cited by 9
Hennessey, R. C., & Brown, K. M. (2021) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.11.010 · Cited by 10
Replication Timing Becomes Intertwined with 3D Genome Organization
Ma, J., & Duan, Z. (2019) · Cell · doi:10.1016/j.cell.2019.01.027 · Cited by 10
“In addition, A/B compartments and TADs are established under different mechanisms, with CTCF and cohesin only responsible for CTCF-dependent TAD formations (Nora et al., 2017; Rao et al., 2017; Schwarzer et al., 2017).”
Cohesin disrupts polycomb-dependent chromosome interactionsPreprint
Rhodes, J., Feldmann, A., Hernández-Rodríguez, B., Díaz, N., Brown, J., Fursova, N. A., Blackledge, N. P., Prathapan, P., Dobrinić, P., Huseyin, M. K., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/593970 · Cited by 10
“Cohesin counteracts polycomb chromatin domain interactions independently of TADs and insulation (A) A schematic illustrating the genotype of the CTCF-AID-GFP cell line (Nora et al., 2017).”
BackgroundMethodInfluentialCis-regulatory chromatin contacts form de novo in the absence of loop extrusionPreprint
Aboreden, N. G., Zhao, H., Shan, F., Liu, F., Zhang, H., & Blobel, G. A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.12.632634 · Cited by 10
Human Body Single-Cell Atlas of 3D Genome Organization and DNA MethylationPreprint
Zhou, J., Wu, Y., Liu, H., Tian, W., Castanon, R., Bartlett, A., Zhang, Z., Yao, G., Shi, D., Clock, B., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.23.644697 · Cited by 10
Synchronization of the segmentation clock using synthetic cell–cell signalingPreprint
Isomura, A., Asanuma, D., & Kageyama, R. (2025) · Genes & Development · doi:10.1101/gad.352538.124 · Cited by 11
“We modified a targeting vector to introduce an expression cassette at the mouse TIGRE locus (a generous gift from Benoit Bruneau; Addgene 92142) (Nora et al. 2017).”
An updated catalog of CTCF variants associated with neurodevelopmental disorder phenotypes
Price, E., Fedida, L. M., Pugacheva, E. M., Ji, Y. J., Loukinov, D. I., & Lobanenkov, V. V. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1185796 · Cited by 9
“Depletion of CTCF in mammalian cell lines using the auxin-inducible degron system results in loss of chromatin looping and limited effects on gene transcription (Nora et al., 2017; Hyle et al., 2023).”
BackgroundFrom Genotype to Phenotype: How Enhancers Control Gene Expression and Cell Identity in Hematopoiesis
Mulet‐Lazaro, R., & Delwel, R. (2023) · HemaSphere · doi:10.1097/hs9.0000000000000969 · Cited by 11
“While CTCF is present at the vast majority of TAD boundaries, it is only found at a small fraction of E-P loops.”
BackgroundInfluentialCellular zinc status alters chromatin accessibility and binding of p53 to DNA
Ocampo, D., Damon, L. J., Sanford, L., Holtzen, S. E., Jones, T., Allen, M. A., Dowell, R. D., & Palmer, A. E. (2024) · Life Science Alliance · doi:10.26508/lsa.202402638 · Cited by 12
“Changes to the labile Zn 2+ pool that affect CTCF ’ s function could disrupt TADs, as it was shown that CTCF degradation in mouse embryonic stem cells distorts TAD architecture (Nora et al, 2017), rendering potential changes to chromatin accessibility.”
BackgroundShao, L., Yu, H., Wang, M., Chen, L., Ji, B., Wu, T. Q., Teng, X., Su, M., Han, X., Shi, W., et al. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06915-z · Cited by 9
“Therefore, this study has potential clinical application in precision medicine of PDAC, and also establishes a solid theoretical foundation for gaining deeper insights into the pathogenesis of PDAC.”
BackgroundCohesin positions the epigenetic reader Phf2 within the genome
Tang, W., Costantino, L., Stocsits, R. R., Wutz, G., Ladurner, R., Hudecz, O., Mechtler, K., & Peters, J. (2025) · The EMBO Journal · doi:10.1038/s44318-024-00348-2 · Cited by 9
“Most TAD boundaries depend on the DNA binding protein CTCF (Nora et al, 2017; Wutz et al, 2017), which stops cohesin-mediated loop extrusion (Davidson et al, 2023; Zhang et al, 2023), but the replicative MCM helicase (Dequeker et al, 2022) and active genes (Banigan et al, 2023) are also cohesin…”
Pioneer factor GATA6 promotes colorectal cancer through 3D genome regulation
Lyu, H., Chen, X., Cheng, Y., Zhang, T.-S., Wang, P., Wong, J. H.-Y., Wang, J., Stasiak, L. A., Sun, L., Yang, G., et al. (2025) · Science Advances · doi:10.1126/sciadv.ads4985 · Cited by 9
The Dance of Promoters and Enhancers in Gene Regulation: Fast or Slow, Entwined or Distant?
Nazarova, M., & Sexton, T. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169223 · Cited by 10
Metelova, M., Vigh, M. L., & Krietenstein, N. (2025) · Nature Communications · doi:10.1038/s41467-025-64350-w · Cited by 11
“Despite extensive evidence supporting the role of chromatin architectural proteins in E-P/P-P interactions 14,16,54,55 , recent high-resolution studies report minimal alterations in the E-P/P-P connectome following their depletion 2,22,48 .”
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
About these checks
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 ›
Are you an author, or do you see a problem with this page? Request a review
