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 701–800 of 1,001
The Functions and Mechanisms of Action of Insulators in the Genomes of Higher Eukaryotes
Melnikova, L. S., Georgiev, P. G., & Golovnin, A. K. (2020) · Acta Naturae · doi:10.32607/actanaturae.11144 · Cited by 24
Kenter, A. L., Watson, C. T., & Spille, J.-H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.682589 · Cited by 21
“However, while sharp TAD boundaries are lost upon CTCF inactivation, compartment organization as well as TAD-like globular chromatin domain structures are preserved in single cell experiments (53) and the impact of CTCF inactivation on the transcriptome is small (54).”
BackgroundUncovering the Principles of Genome Folding by 3D Chromatin ModelingPreprint
Yıldırım, A., Boninsegna, L., Zhan, Y., & Alber, F. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a039693 · Cited by 25
Mach, P., Kos, P., Zhan, Y., Cramard, J., Gaudin, S., Tünnermann, J., Marchi, E., Eglinger, J., Zuin, J., Kryzhanovska, M., et al. (2022) · bioRxiv · doi:10.1101/2022.03.03.482826 · Cited by 18
Self-citationDynamic nucleosome remodeling mediated by YY1 underlies early mouse developmentPreprint
Sakamoto, M., Abe, S., Miki, Y., Miyanari, Y., Sasaki, H., & Ishiuchi, T. (2023) · Genes & Development · doi:10.1101/gad.350376.122 · Cited by 24
“…Yy1 KD on the transcriptome of eight-Sakamoto cell embryos was minimal, which is highly reminiscent of the limited effect of the depletion of chromatin structural proteins YY1 or CTCF on gene expression in other cell types (Nora et al. 2017; Hyle et al. 2019; Andreu et al. 2022; Hsieh et al. 2022).”
BackgroundCohesin guides homology search during DNA repair using loops and sister chromatid linkages
Teloni, F., Takács, Z., Mitter, M., Langer, C. C. H., Prlesi, I., Steinacker, T. L., Reuter, V. P., Mylarshchikov, D. E., & Gerlich, D. W. (2025) · Science · doi:10.1126/science.adw0566 · Cited by 28
Large-scale chromatin organisation in interphase, mitosis and meiosis
MacGregor, I. A., Adams, I. R., & Gilbert, N. (2019) · Biochemical Journal · doi:10.1042/bcj20180512 · Cited by 23
The Dynamic 3D Genome in Gametogenesis and Early Embryonic Development
Li, F., An, Z., & Zhang, Z. (2019) · Cells · doi:10.3390/cells8080788 · Cited by 21
Daban, J. (2019) · FEBS Letters · doi:10.1002/1873-3468.13724 · Cited by 21
Decoding the organization, dynamics, and function of the 4D genome
Aboelnour, E., & Bonev, B. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.04.023 · Cited by 24
Soibam, B., & Zhamangaraeva, A. (2021) · BMC Genomics · doi:10.1186/s12864-021-07727-7 · Cited by 20
In silico discovery of repetitive elements as key sequence determinants of 3D genome folding
Gunsalus, L. M., Keiser, M. J., & Pollard, K. S. (2023) · Cell Genomics · doi:10.1016/j.xgen.2023.100410 · Cited by 22
Loss of cohesin regulator PDS5A reveals repressive role of Polycomb loops
Bsteh, D., Moussa, H. F., Michlits, G., Yelagandula, R., Wang, J.-K., Elling, U., & Bell, O. (2021) · bioRxiv · doi:10.1038/s41467-023-43869-w · Cited by 19
Mata-Garrido, J., Tapia, O., Casafont, Í., Berciano, M. T., Cuadrado, A., & Lafarga, M. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0573-6 · Cited by 24
“CTCF is an insulator protein that, together with cohesin complex, is responsible for the chromatin folding in Topologically Associating Domains (TADs), submegabase segments that tend to self-associate and define discrete transcriptionally related regions [17, 46, 54].”
BackgroundLocal chromatin interactions contribute to expression of the fibrinogen gene cluster
Jaimes, C. E., Fish, R. J., & Neerman‐Arbez, M. (2018) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.14248 · Cited by 21
Pavlaki, I., Docquier, F., Chernukhin, I. V., Kita, G.-X., Gretton, S., Clarkson, C. T., Teif, V. B., & Klenova, E. M. (2018) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2018.06.010 · Cited by 21
The matrix revolutions: towards the decoding of the plant chromatin three-dimensional reality
Huang, Y., Rodriguez‐Granados, N. Y., Latrasse, D., Raynaud, C., Benhamed, M., & Ramirez-Prado, J. S. (2020) · Journal of Experimental Botany · doi:10.1093/jxb/eraa322 · Cited by 21
Fiorillo, L., Bianco, S., Esposito, A., Conte, M., Sciarretta, R., Musella, F., & Chiariello, A. M. (2019) · Wiley Interdisciplinary Reviews Computational Molecular Science · doi:10.1002/wcms.1454 · Cited by 24
“At the sub-megabase scale chromatin tend to form domains of enriched interactions, commonly named topologically associated domains (TADs).(13,14) Importantly, whether TADs are universal and stable features across single cells is still object of intense debates.”
BackgroundDiscovering a binary CTCF code with a little help from BORIS
Lobanenkov, V. V., & Zentner, G. E. (2017) · Nucleus · doi:10.1080/19491034.2017.1394536 · Cited by 21
“TADs are megabase-scale segments of the genome displaying high levels of self-interaction that are dependent on CTCF for proper folding.(37) Disruption of TADs is associated with activation of proto-oncogenes in cancers including T-cell acute lymphoblastic leukemia,(38) glioma,(39) and colorectal carcinoma.”
BackgroundDynamics of nuclear architecture during early embryonic development and lessons from liveimaging
Pecori, F., & Torres‐Padilla, M. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.02.018 · Cited by 20
The impact of the embryonic DNA methylation program on CTCF-mediated genome regulation
Monteagudo, A., Albert, J. R., Scarpa, M., Noordermeer, D., & Greenberg, M. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae724 · Cited by 22
“It is known that CTCF plays a role together with the cohesin complex in the demarcation of TADs boundaries ( 16–18 ) and also has a role in transcription as it regulates loops between enhancers and promoters ( 19 ,20 ).”
BackgroundMethodG9a/GLP-Sensitivity of H3K9me2 Demarcates Two Types of Genomic Compartments
Yan, Z., Ji, L., Huo, X., Wang, Q., Zhang, Y., & Wen, B. (2020) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2020.08.001 · Cited by 19
“Through quantification with the duplicates of Hi-C data, we showed that compartmentalization strength [31], increased by 23%, from 3.495 to 4.31, upon G9a/GLP inhibition (Figure 4C).”
InfluentialChromatin Alterations in Neurological Disorders and Strategies of (Epi)Genome Rescue
Janowski, M., Milewska, M., Zare, P., & Pękowska, A. (2021) · Pharmaceuticals · doi:10.3390/ph14080765 · Cited by 21
Cell cycle dynamics and developmental dynamics of the 3D genome: toward linking the two timescales
Miura, H., & Hiratani, I. (2022) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2021.101898 · Cited by 21
Effects of Transcription-Dependent Physical Perturbations on the Chromosome Dynamics in Living Cells
Ku, H., Park, G., Goo, J., Lee, J., Park, T. L., Shim, H., Kim, J. H., Cho, W., & Jeong, C. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.822026 · Cited by 18
Long interspersed nuclear element 1 and B1/Alu repeats blueprint genome compartmentalization
Li, S., & Shen, X. (2023) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2023.102049 · Cited by 20
CTCF and cellular heterogeneity
Ren, G., & Zhao, K. (2019) · Cell & Bioscience · doi:10.1186/s13578-019-0347-2 · Cited by 20
Genome organization via loop extrusion, insights from polymer physics models
Ghosh, S. K., & Jost, D. (2019) · Briefings in Functional Genomics · doi:10.1093/bfgp/elz023 · Cited by 24
“For example, in the absence of BEs, models predict the disappearance of corner peaks and corresponding TADs but the maintenance of the scaling laws and even their extension beyond the former TAD boundaries, in agreement with CTCF knock-down experiments [43].”
ResultStutzman, A. V., Liang, A. S., Beilinson, V., & Ikegami, K. (2020) · Epigenetics & Chromatin · doi:10.1186/s13072-019-0325-2 · Cited by 20
“In vertebrates, CTCF has a central role in defining TAD boundaries and is essential for development [11,59,60].”
BackgroundPerez-Rico, Y. A., Barillot, E., & Shkumatava, A. (2020) · iScience · doi:10.1016/j.isci.2020.101046 · Cited by 19
Chd8 regulates X chromosome inactivation in mouse through fine-tuning control of Xist expression
Cerase, A., Young, A. N., Ruiz, N. B., Buneß, A., Sant, G. M., Arnold, M., Giacomo, M. D., Ascolani, M., Kumar, M., Hierholzer, A., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-01945-1 · Cited by 20
Complementary chromosome folding by transcription factors and cohesinPreprint
Pereira, M. C. F., Brackley, C. A., Michieletto, D., Annunziatella, C., Bianco, S., Chiariello, A. M., Nicodemi, M., & Marenduzzo, D. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/305359 · Cited by 19
Live-Cell Imaging Reveals Enhancer-dependent Sox2 Transcription in the Absence of Enhancer ProximityPreprint
Alexander, J. M., Guan, J., Huang, B., Lomvardas, S., & Weiner, O. D. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/409672 · Cited by 20
“…bright flashes of MS2cp signal in the ESC nucleus, which occurred in spatial proximity to the cuO and tetO labels, and were similar to the MS2 transcriptional bursts observed else-where ( Bothma et al., 2014 ; Chubb et al., 2006 ; Lionnet et al., 2011 ; Martin et al., 2013 ; Ochiai et al., 2014 ).”
BackgroundResultAgrawal, P., Heimbruch, K. E., & Rao, S. (2018) · Comprehensive physiology · doi:10.1002/cphy.c180028 · Cited by 27
A functional overlap between actively transcribed genes and chromatin boundary elementsPreprint
Harrold, C. L., Gosden, M. E., Hanssen, L. L. P., Stolper, R. J., Downes, D. J., Telenius, J. M., Biggs, D., Preece, C., Alghadban, S., Sharpe, J. A., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.01.182089 · Cited by 18
“CTCF results in a loss (32, 33) or weakening (34) of ~80% of TADs across the genome; but 66 not all TADs depend on CTCF.”
BackgroundThe Impact of Space and Time on the Functional Output of the GenomePreprint
Nollmann, M., Bennabi, I., Götz, M., & Gregor, T. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a040378 · Cited by 23
“For example, 3D loops between converging CTCF sites can produce specific 3D interactions between TAD borders (Rao et al. 2015) while cohesin-mediated loops can affect the contact frequencies within TADs (Nora et al. 2017; Rao et al. 2017).”
BackgroundInfluentialMultilayer organization of chromosomes
Daban, J. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823579-9.00010-2 · Cited by 19
Ealo, T., Sánchez-Gaya, V., Respuela, P., Martín, M. M., Martín-Batista, E., Haro, E., & Rada-Iglesias, Á. (2024) · Nature Communications · doi:10.1038/s41467-024-51602-4 · Cited by 24
“Furthermore, although architectural proteins play a preponderant role in TAD boundary formation, with, for example, over 80% of mammalian TAD boundaries being CTCF dependent, they seem to be dispensable for or even counteract the organization of chromatin compartments 11,15,16 .”
InfluentialBeyond genomic weaving: molecular roles for CTCF outside cohesin loop extrusion
Corin, A. J., Nora, E. P., & Ramani, V. (2024) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2024.102298 · Cited by 19
Self-citationUV-induced reorganization of 3D genome mediates DNA damage response
Kaya, V. O., & Adebalı, O. (2025) · Nature Communications · doi:10.1038/s41467-024-55724-7 · Cited by 19
“As per the existing theory regarding TAD formation, genome regions are dynamically gathered within TADs via loop extrusion facilitated by the cohesin complex until an insulator protein like CTCF obstructs the extrusion process 40 – 43 .”
Fritz, A. J., Gillis, N. E., Gerrard, D. L., Rodriguez, P. D., Hong, D., Rose, J. T., Ghule, P. N., Bolf, E. L., Gordon, J. A., Tye, C. E., et al. (2019) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22731 · Cited by 19
“Although the segregation of A and B compartments generally occurs at TAD boundaries, knockdown of cohesin and/or CTCF did not affect A and B compartmentalization.(116,118) While CTCF plays a major role in chromatin organization, its absence at many TAD boundaries suggests alternative mechanisms, including epigenetic m…”
BackgroundMethodThe deubiquitinase Usp9x regulates PRC2-mediated chromatin reprogramming during mouse development
Macrae, T. A., & Ramalho‐Santos, M. (2021) · Nature Communications · doi:10.1038/s41467-021-21910-0 · Cited by 16
Galan, S., Serra, F., & Martı́-Renom, M. A. (2022) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqac021 · Cited by 18
“It suggests that CTCF and cohesin play a role in TAD and loop formation, but not necessarily in genome compartmentalization (14,15).”
BackgroundAltering enhancer–promoter linear distance impacts promoter competition in cis and in trans
Bateman, J. R., & Johnson, J. E. (2022) · Genetics · doi:10.1093/genetics/iyac098 · Cited by 19
Fritz, A. J., Dika, M. E., Toor, R. H., Rodriguez, P. D., Foley, S. J., Ullah, R., Nie, D., Banerjee, B., Lohese, D., Tracy, K. M., et al. (2022) · Results and problems in cell differentiation · doi:10.1007/978-3-031-06573-6_12 · Cited by 23
Remembering through the genome: the role of chromatin states in brain functions and diseases
Arzate‐Mejía, R. G., & Mansuy, I. M. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02415-4 · Cited by 22
“Remarkably, genomic regions with lasting changes in chromatin accessibility are also engaged in persistent long-range interactions that are independent of CTCF binding.”
BackgroundInfluentialRNA polymerase II pausing regulates chromatin organization in erythrocytes
Pénagos-Puig, A., Claudio-Galeana, S., Stephenson-Gussinye, A., Jácome-López, K., Aguilar-Lomas, A., Chen, X., Pérez-Molina, R., & Furlan-Magaril, M. (2023) · Nature Structural & Molecular Biology · doi:10.1038/s41594-023-01037-0 · Cited by 16
Messina, O., Raynal, F., Gurgo, J., Fiche, J.-B., Pancaldi, V., & Nöllmann, M. (2023) · Nature Communications · doi:10.1038/s41467-023-42485-y · Cited by 19
“In Drosophila , ensemble analysis showed that adjacent TAD borders tend to preferentially interact 20 , however contact maps do not display focal chromatin peaks as those observed in mammals 7,34,35 .”
ZNF143 deletion alters enhancer/promoter looping and CTCF/cohesin geometry
Zhang, M., Huang, H., Li, J., & Wu, Q. (2024) · Cell Reports · doi:10.1016/j.celrep.2023.113663 · Cited by 20
Hu, J.-X., Song, L., Ning, M., Niu, X., Han, M., Gao, C.-Z., Feng, X., Cai, H., Li, T., Li, F., et al. (2024) · BMC Biology · doi:10.1186/s12915-024-01817-0 · Cited by 15
Cohesin regulation and roles in chromosome structure and function
Rittenhouse, N., & Dowen, J. M. (2024) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2024.102159 · Cited by 19
Structural–Functional Domains of the Eukaryotic Genome
Razin, S. V., & Gavrilov, A. A. (2018) · Biochemistry (Moscow) · doi:10.1134/s0006297918040028 · Cited by 20
“The inhibition of experssion and induced degradation of CTCF have the same effect [88, 89].”
BackgroundJi, L.-Z., Huo, X., Zhang, Y., Yan, Z., Wang, Q.-F., & Wen, B. (2020) · Biochimica et Biophysica Acta. Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2020.194518 · Cited by 14
Effective model of loop extrusion predicts chromosomal domains
Crippa, M., Zhan, Y., & Tiana, G. (2020) · Physical review. E · doi:10.1103/physreve.102.032414 · Cited by 21
Physical mechanisms of chromatin spatial organization
Chiariello, A. M., Bianco, S., Esposito, A., Fiorillo, L., Conte, M., Irani, E., Musella, F., Abraham, A., Prisco, A., & Nicodemi, M. (2021) · FEBS Journal · doi:10.1111/febs.15762 · Cited by 20
Warwick, T., Schulz, M. H., Gilsbach, R., Brandes, R. P., & Seuter, S. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac178 · Cited by 16
Integrative studies of 3D genome organization and chromatin structure
Stefano, M. D., & Cavalli, G. (2022) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2022.102493 · Cited by 23
3D or Not 3D: Shaping the Genome during DevelopmentPreprint
Glaser, J., & Mundlos, S. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a040188 · Cited by 18
Epigenetic and 3D genome reprogramming during the aging of the human hippocampus
Zemke, N. R., Lee, S. Y., Mamde, S., Yang, B., Berchtold, N. C., Garduño, B. M., Indralingam, H. S., Bartosik, W. M., Lau, P. K., Dong, K., et al. (2026) · Science · doi:10.1126/science.adt8307 · Cited by 32
Rare or Overlooked? Structural Disruption of Regulatory Domains in Human Neurocristopathies
Sánchez-Gaya, V., Mariner-Faulí, M., & Rada-Iglesias, Á. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00688 · Cited by 17
Yunusova, A., Smirnov, A. V., Шнайдер, Т. А., Lukyanchikova, V., Afonnikova, S. D., & Баттулин, Н. Р. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.757394 · Cited by 18
“This approach is recommended in majority of protocols where many suitable loci (H11, TIGRE, AAVS1, and Rosa26) were extensively characterized (Baker et al., 2016; Nora et al., 2017; Pryzhkova et al., 2020).”
BackgroundInfluentialRodríguez, S., Scadden, A. W., Reckard, A. T., Shtanko, Y., Hull-Crew, C., & Klocko, A. D. (2022) · G3 Genes Genomes Genetics · doi:10.1093/g3journal/jkac053 · Cited by 18
Parteka-Tojek, Z., Zhu, J. J., Lee, B., Jodkowska, K., Wang, P., Aaron, J., Chew, T., Banecki, K. H., Plewczyński, D., & Ruan, Y. (2022) · Scientific Reports · doi:10.1038/s41598-022-12568-9 · Cited by 21
Drosophila insulator proteins exhibit in vivo liquid–liquid phase separation properties
Amankwaa, B., Schoborg, T. A., & Labrador, M. (2022) · Life Science Alliance · doi:10.26508/lsa.202201536 · Cited by 19
“…CTCF sites in the DNA allows long-range contacts between genomic regions normally belonging to separated TADs with sometimes pathological implications, including abnormal limb development and cancer (Soshnikova et al, 2010; Lupi´añez et al, 2015; Nora et al, 2017; Ibrahim & Mundlos, 2020).”
BackgroundModulation of the high-order chromatin structure by Polycomb complexes
Guo, Y., & Wang, G. G. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1021658 · Cited by 19
“In contrast, TADs are often anchored by CTCF (Nora et al., 2017; Hansen et al., 2018).”
BackgroundConsiderations and caveats for analyzing chromatin compartments
Kalluchi, A., Harris, H. L., Reznicek, T. E., & Rowley, M. J. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1168562 · Cited by 18
Emerging insights into enhancer biology and function
Arnold, M., & Stengel, K. R. (2023) · Transcription · doi:10.1080/21541264.2023.2222032 · Cited by 20
“Moreover, transcriptional changes following CTCF or cohesin degradation become apparent only with a delay and are limited to a small number of genes [130,132], arguing against a direct and global effect of chromatin architecture on gene expression in the tested cell systems.”
BackgroundMachine and Deep Learning Methods for Predicting 3D Genome Organization
Wall, B. P. G., Nguyen, M., Harrell, J. C., & Dozmorov, M. G. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-4136-1_22 · Cited by 20
TAD border deletion at the Kit locus causes tissue-specific ectopic activation of a neighboring gene
Kabirova, E., Ryzhkova, A., Lukyanchikova, V., Khabarova, A. A., Korablev, A. N., Шнайдер, Т. А., Nuriddinov, M., Belokopytova, P. S., Smirnov, A. V., Хоцкин, Н. В., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48523-7 · Cited by 19
“Although altered TADs architecture is indeed associated with some pathogenicphenotypes 9,10 , genome wide disappearanceof TADs insulation upon CTCF or cohesin depletion does not cause global transcriptional effects 11,12 .”
BackgroundDo, C., Jiang, G., Cova, G., Katsifis, C. C., Narducci, D. N., Sakellaropoulos, T., Vidal, R. S., Lhoumaud, P., Tsirigos, A., Regis, F. F., et al. (2025) · Cell Genomics · doi:10.1016/j.xgen.2025.100813 · Cited by 20
“14,15 To ask whether this could be explained by indirect effects that depend on cell-specific transcriptomes, we estimated the direct versus indirect effects of CTCF mutations on gene expression.”
Self-citation3D Genome Organization Influences the Chromosome Translocation Pattern
McCord, R. P., & Balajee, A. S. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-0593-1_8 · Cited by 18
Lesne, A., Baudement, M.-O., Rebouissou, C., & Forné, T. (2019) · Genes · doi:10.3390/genes10121049 · Cited by 20
“While cohesin and CTCF proteins are required for TAD organization, these factors are dispensable for the maintenance of chromosomal compartments, which rely on di ff erent organization principle [13–15].”
HiC1Dmetrics: framework to extract various one-dimensional features from chromosome structure data
Wang, J., & Nakato, R. (2021) · Briefings in Bioinformatics · doi:10.1093/bib/bbab509 · Cited by 17
“To estimate the reproducibility of 1D metrics under different conditions, we utilized three publicly available Hi-C datasets for three murine studies: Data1 (GSE93431) contains Hi-C data for the cohesin loader Nipbl knockout (two replicates) and non-treated hepatocytes (four replicates) [25]; Data2 (GSE96107) contains…”
MethodDNA Replication Timing Enters the Single-Cell Era
Hiratani, I., & Takahashi, S. (2019) · Genes · doi:10.3390/genes10030221 · Cited by 21
“TAD structure, however, is not absolutely necessary to properly sort individual domains into A or B compartments [71,72] or for maintaining proper replication timing profiles [73].”
BackgroundCondensin II inactivation in interphase does not affect chromatin folding or gene expressionPreprint
Abdennur, N. A., Schwarzer, W., Pękowska, A., Shaltiël, I. A., Huber, W. K., Haering, C. H., Mirny, L. A., & Spitz, F. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/437459 · Cited by 19
Self-citationThe logic of native enhancer-promoter compatibility and cell-type-specific gene expression variationPreprint
Narita, T., Higashijima, Y., Kilic, S., Maskey, E., Neumann, K., & Choudhary, C. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.18.500456 · Cited by 17
Cohesin is required for long-range enhancer action
Kane, L., Williamson, I., Flyamer, I. M., Kumar, Y., Hill, R. E., Lettice, L. A., & Bickmore, W. A. (2021) · doi:10.1101/2021.06.24.449812 · Cited by 23
Mechanisms of Enhancer-Mediated Gene Activation in the Context of the 3D Genome
Papantonis, A., & Oudelaar, A. M. (2025) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-120423-012301 · Cited by 19
Epigenetic networks coordinate DNA methylation across the genome
Wagner, W. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.06.037 · Cited by 20
“110,111 Furthermore, lamina-associated domains (LADs) are genomic regions anchored to the nuclear lamina—a dense fibrillar network located just beneath the inner nuclear membrane.”
Logic and lineage impacts on functional transcription factor deployment for T-cell fate commitment
Rothenberg, E. V. (2021) · Biophysical Journal · doi:10.1016/j.bpj.2021.04.002 · Cited by 17
“Elegant experiments in which cohesin or CTCF was acutely degraded in tissue culture cells or in noncycling thymocytes (to filter out confounding population effects due to cohesin roles in mitosis) showed that while loss of these components rapidly dissociated loops, a large fraction of the cell-type specific gene expr…”
BackgroundThe Causes and Consequences of Spatial Organization of the Genome in Regulation of Gene Expression
Agelopoulos, M., Foutadakis, S., & Thanos, D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.682397 · Cited by 19
“Despite the established roles of the architectural protein CTCF in supporting regulatory enhancer-promoter interactions (66, 73), its depletion although leads to a significant reduction of TAD structures results in moderate rather than dramatic changes in global gene expression (77, 78).”
BackgroundZhang, X., & Wang, T. (2021) · Plant and Cell Physiology · doi:10.1093/pcp/pcab134 · Cited by 18
Chromatin Hubs: A biological and computational outlook
Mora, A., Huang, X., Jauhari, S., Jiang, Q. L., & Li, X. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.07.002 · Cited by 18
“CTCF depletion effects can be observed in (cid:1) 80% of TAD boundaries [15].”
BackgroundRegulation of cohesin‐mediated chromosome folding by PDS5 in mammals
Yu, D., Chen, G., Wang, Y., Wang, Y., Lin, R., Liu, N., Zhu, P., Liu, H., Hu, T., Feng, R., et al. (2022) · EMBO Reports · doi:10.15252/embr.202254853 · Cited by 15
“This is consistent with the notion that compartments arise from different mechanisms independent of cohesin and CTCF (Nora et al , 2017; Schwarzer et al , 2017).”
Hi-TrAC detects active sub-TADs and reveals internal organizations of super-enhancers
Cao, Y., Liu, S., Cui, K., Tang, Q., & Zhao, K. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad378 · Cited by 18
Transcription induces context-dependent remodeling of chromatin architecture during differentiation
Chahar, S., Zouari, Y. B., Salari, H., Molitor, A. M., Kobi, D., Maroquenne, M., Erb, C., Mossler, A., Karasu, N., Jost, D., et al. (2023) · PLoS Biology · doi:10.1371/journal.pbio.3002424 · Cited by 19
Attraction and disruption: how loop extrusion and compartmentalisation shape the nuclear genome
Magnitov, M. D., & de Wit, E. (2024) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2024.102194 · Cited by 16
Liu, C., Nagashima, H., Fernando, N., Bass, V., Gopalakrishnan, J., Signorella, S., Montgomery, W., Lim, A. I., Harrison, O. J., Reich, L. N., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.04.007 · Cited by 18
Sasaki, M., Kato, D., Murakami, K., Yoshida, H., Takase, S., Otsubo, T., & Ogiwara, H. (2024) · Nature Communications · doi:10.1038/s41467-024-49063-w · Cited by 17
“CTCF (CCCTC-binding factor) is a transcription factor that localizes upstream of its target gene loci 40 .”
Niharika, N., Ureka, L., Roy, A., & Patra, S. K. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2024.189136 · Cited by 18
The impact of transcription-mediated replication stress on genome instability and human disease
Gnan, S., Liu, Y., Spagnuolo, M., & Chen, C.-L. (2020) · Genome Instability & Disease · doi:10.1007/s42764-020-00021-y · Cited by 16
“Conversely, knock-outs or knock-downs of several other nuclear structural proteins, such as cohesin or CTCF, alter chromatin structure but not RT (Oldach and Nieduszynski 2019; Rao et al. 2017; Sima et al. 2019; Nora et al. 2017).”
BackgroundFernandez, L. R., Gilgenast, T. G., & Phillips‐Cremins, J. E. (2020) · Genome biology · doi:10.1186/s13059-020-02061-9 · Cited by 17
Epigenetics and Heart Development
George, R. M., & Firulli, A. B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.637996 · Cited by 16
An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation
Bhat, K. H., Priyadarshi, S., Naiyer, S., Qu, X., Farooq, H., Kleiman, E., Xu, J., Lei, X., Cantillo, J. F., Wuerffel, R., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36414-2 · Cited by 18
New insights emerge as antibody repertoire diversification meets chromosome conformation
Kenter, A. L., & Feeney, A. J. (2019) · F1000Research · doi:10.12688/f1000research.17358.1 · Cited by 17
Shah, R., Tortora, M. M. C., Louafi, N., Rahmaninejad, H., Hansen, K. L., Anderson, E. C., Wen, D., Giorgetti, L., Fudenberg, G., & Nora, E. P. (2025) · doi:10.1101/2025.08.14.667581 · Cited by 15
Self-citationNarita, T., Kilic, S., Higashijima, Y., Scherer, N. M., Pappas, G., Maskey, E., & Choudhary, C. (2025) · Nature Genetics · doi:10.1038/s41588-025-02404-x · Cited by 20
“CTCF-regulated genes were quantified in mESCs after acute depletion of Ctcf-mAid-Gfp (CTCF AID ) 26 (Extended Data Fig.”
InfluentialKang, J. G., Kim, Y. W., Park, S., Kang, Y., & Kim, A. (2021) · The FASEB Journal · doi:10.1096/fj.202100105rr · Cited by 16
Chromatin Organization and Function in Drosophila
Llorens‐Giralt, P., Camilleri‐Robles, C., Corominas, M., & Climent‐Cantó, P. (2021) · Cells · doi:10.3390/cells10092362 · Cited by 16
Cummings, C. T., & Rowley, M. J. (2022) · Genes · doi:10.3390/genes13040583 · Cited by 15
“Addition of the AID tag to CTCF or cohesin resulted in partial depletion by about half, even in the absence of auxin addition [18,33,35,36].”
BackgroundMethodInfluential
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
