Evidence map›Paper›PMID 31910870›Full record

ArticleGenome biology2020

Clustered CTCF binding is an evolutionary mechanism to maintain topologically associating domains.

Elissavet Kentepozidou, Sarah J Aitken, Christine Feig, Klara Stefflova, Ximena Ibarra-Soria, Duncan T Odom, Maša Roller, Paul Flicek

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

83 citing papers in PubMed, 128 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Evolution of CTCF binding sites in the human genome.Molecular biology and evolution · 2026
    Article
  6. Review
  7. Article
  8. High-throughputbioRxiv : the preprint server for biology · 2025
    Article
  9. Review
  10. Review
  11. Genome-wide rules of transcription factor cooperativity revealed throughbioRxiv : the preprint server for biology · 2025
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 3 countries.

Elissavet KentepozidouEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, CB10 1SD, UK.
Sarah J AitkenCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Christine FeigCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Klara StefflovaCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Ximena Ibarra-SoriaCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Duncan T OdomCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Maša RollerEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, CB10 1SD, UK. roller@ebi.ac.uk.
Paul FlicekEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, CB10 1SD, UK. flicek@ebi.ac.uk.ORCID 0000-0002-3897-7955
University of Cambridge · GBEuropean Bioinformatics Institute · GBGerman Cancer Research Center · DE

Funding

Cancer Research UK 20412Cancer Research UK 22398European Research Council 615584Wellcome Trust 202878/Z/16/ZWellcome Trust WT106563/Z/14Wellcome Trust WT108749/Z/15/ZWellcome Trust WT202878/B/16/ZWellcome Trust WT202878/Z/16/Z
6 · The paper itself

Abstract

backgroundCTCF binding contributes to the establishment of a higher-order genome structure by demarcating the boundaries of large-scale topologically associating domains (TADs). However, despite the importance and conservation of TADs, the role of CTCF binding in their evolution and stability remains elusive.

resultsWe carry out an experimental and computational study that exploits the natural genetic variation across five closely related species to assess how CTCF binding patterns stably fixed by evolution in each species contribute to the establishment and evolutionary dynamics of TAD boundaries. We perform CTCF ChIP-seq in multiple mouse species to create genome-wide binding profiles and associate them with TAD boundaries. Our analyses reveal that CTCF binding is maintained at TAD boundaries by a balance of selective constraints and dynamic evolutionary processes. Regardless of their conservation across species, CTCF binding sites at TAD boundaries are subject to stronger sequence and functional constraints compared to other CTCF sites. TAD boundaries frequently harbor dynamically evolving clusters containing both evolutionarily old and young CTCF sites as a result of the repeated acquisition of new species-specific sites close to conserved ones. The overwhelming majority of clustered CTCF sites colocalize with cohesin and are significantly closer to gene transcription start sites than nonclustered CTCF sites, suggesting that CTCF clusters particularly contribute to cohesin stabilization and transcriptional regulation.

conclusionsDynamic conservation of CTCF site clusters is an apparently important feature of CTCF binding evolution that is critical to the functional stability of a higher-order chromatin structure.

Indexed as

Evolution, MolecularAnimalsCCCTC-Binding FactorChromatinChromatin Immunoprecipitation SequencingGenomeMiceCCCTC-Binding FactorChromatinCtcf protein, mouseChromatin architectureCross-species analysisCTCF binding evolutionTADs

Identifiers

PMID31910870
PMCPMC6945661
OpenAlexW3009045514

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.