Comprehensive identification and annotation of cell type-specific and ubiquitous CTCF-binding sites in the human genome
Open accessAbstract
Chromatin insulators are DNA elements that regulate the level of gene expression either by preventing gene silencing through the maintenance of heterochromatin boundaries or by preventing gene activation by blocking interactions between enhancers and promoters. CCCTC-binding factor (CTCF), a ubiquitously expressed 11-zinc-finger DNA-binding protein, is the only protein implicated in the establishment of insulators in vertebrates. While CTCF has been implicated in diverse regulatory functions, CTCF has only been studied in a limited number of cell types across human genome. Thus, it is not clear whether the identified cell type-specific differences in CTCF-binding sites are functionally significant. Here, we identify and characterize cell type-specific and ubiquitous CTCF-binding sites in the human genome across 38 cell types designated by the Encyclopedia of DNA Elements (ENCODE) consortium. These cell type-specific and ubiquitous CTCF-binding sites show uniquely versatile transcriptional functions and characteristic chromatin features. In addition, we confirm the insulator barrier function of CTCF-binding and explore the novel function of CTCF in DNA replication. These results represent a critical step toward the comprehensive and systematic understanding of CTCF-dependent insulators and their versatile roles in the human genome.
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As many as 40-50% of CTCF sites may change in different cell types.
“As many as 40–50% of the CTCF sites may change in different cell types (Chen et al., 2012).”
From Multiscale 3D Genome Rewiring during Mouse Neural Development (2017) · cites this paper as Chen et al., 2012
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Shu, W., Chen, H., Bo, X., & Wang, S. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr443 · Cited by 49 · see citing works
Self-citationThe role of CTCF in regulating nuclear organization
Williams, A., & Flavell, R. A. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080066 · Cited by 49 · see citing works
Vostrov, A. A., Taheny, M. J., & Quitschke, W. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109748200 · Cited by 43 · see citing works
Associating transcription factor-binding site motifs with target GO terms and target genes
Mikael Bodén, A., & Bailey, T. L. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn374 · Cited by 31 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Multiscale 3D Genome Rewiring during Mouse Neural Development
Bonev, B., Mendelson Cohen, N., Szabo, Q., Fritsch, L., Papadopoulos, G. L., Lubling, Y., Xu, X., Lv, X., Hugnot, J.-P., Tanay, A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.043 · Cited by 1,338 · see citing works
CTCF Binding Polarity Determines Chromatin Looping
de Wit, E., Vos, E. S. M., Holwerda, S. J. B., Valdes-Quezada, C., Verstegen, M. J. A. M., Teunissen, H., Splinter, E., Wijchers, P. J., Krijger, P. H. L., & de Laat, W. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.09.023 · Cited by 641 · see citing works
The 3D genome in transcriptional regulation and pluripotency
Gorkin, D. U., Leung, D., & Ren, B. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.05.017 · Cited by 391 · see citing works
Structural Basis for the Versatile and Methylation-Dependent Binding of CTCF to DNA
Hashimoto, H., Wang, D., Horton, J. R., Zhang, X., Corces, V. G., & Cheng, X. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.05.004 · Cited by 268 · see citing works
Saldaña-Meyer, R., González-Buendía, E., Guerrero, G., Narendra, V., Bonasio, R., Recillas-Targa, F., & Reinberg, D. (2014) · Genes & Development · doi:10.1101/gad.236869.113 · Cited by 217 · see citing works
Crossed wires: 3D genome misfolding in human disease
Norton, H. K., & Phillips-Cremins, J. E. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201611001 · Cited by 57 · see citing works
- Authors
- Chen, H., Tian, Y., Shu, W., Bo, X., & Wang, S.
- Affiliations
- Beijing Radiation Center (CN)
- Corresponding author
- Shu, Wenjie
- Bo, Xiaochen
- Wang, Shengqi
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-07-19
- Volume
- 7
- Issue
- 7
- Pages
- e41374
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3400636
- OpenAlex
- W2000626262
- Cited by
- 161
- References
- 96
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 19 · 2023: 11 · 2022: 15 · 2021: 9 · 2020: 16 · 2019: 3 · 2018: 13 · 2017: 8 · 2016: 12 · 2015: 17 · 2014: 13 · 2013: 7 · 2012: 1
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China
- 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 › Epigenetics and DNA Methylation
- Keywords
- CTCF, chromatin insulators, CTCF binding sites, cell type-specific binding, enhancer-promoter interactions, heterochromatin boundaries, DNA replication, transcriptional regulation, chromatin features, human genome
- MeSH terms
- CCCTC-Binding Factor, Binding Sites, Humans, Repressor Proteins, Genome, Human, Insulator Elements
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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