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Characterization of genome-wide enhancer-promoter interactions reveals co-expression of interacting genes and modes of higher order chromatin organization
Open accessAbstract
Recent epigenomic studies have predicted thousands of potential enhancers in the human genome. However, there has not been systematic characterization of target promoters for these potential enhancers. Using H3K4me2 as a mark for active enhancers, we identified genome-wide EP interactions in human CD4(+) T cells. Among the 6 520 long-distance chromatin interactions, we identify 2 067 enhancers that interact with 1 619 promoters and enhance their expression. These enhancers exist in accessible chromatin regions and are associated with various histone modifications and polymerase II binding. The promoters with interacting enhancers are expressed at higher levels than those without interacting enhancers, and their expression levels are positively correlated with the number of interacting enhancers. Interestingly, interacting promoters are co-expressed in a tissue-specific manner. We also find that chromosomes are organized into multiple levels of interacting domains. Our results define a global view of EP interactions and provide a data set to further understand mechanisms of enhancer targeting and long-range chromatin organization. The Gene Expression Omnibus accession number for the raw and analyzed chromatin interaction data is GSE32677.
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“Enhancer-bound proteins are constrained such that they tend to interact only with genes within these CTCF-CTCF loops.”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Chepelev et al., 2012
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“In the models that emerge from these data, each chromosome contains thousands of DNA loops, formed by the interaction of two CTCF molecules bound to different sites, and reinforced by a cohesin molecule (Figure 2A).”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Chepelev et al., 2012
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Metadata
- Authors
- Chepelev, I., Wei, G., Wangsa, D., Tang, Q., & Zhao, K.
- Affiliations
- National Heart, Lung, and Blood Institute (US)
- National Institutes of Health (US)
- Corresponding author
- Zhao, Keji
- Venue
- Cell Research
- Published
- 2012-01-24
- Volume
- 22
- Issue
- 3
- Pages
- 490-503
- ISSN
- 1001-0602 (ISSN-L)
- 1748-7838
- PMC
- PMC3292289
- OpenAlex
- W2154077612
- Cited by
- 253
- References
- 48
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 6 · 2023: 14 · 2022: 23 · 2021: 27 · 2020: 14 · 2019: 21 · 2018: 23 · 2017: 18 · 2016: 20 · 2015: 19 · 2014: 23 · 2013: 19 · 2012: 9
- FWCI
- 8.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- NHLBI Division of Intramural Research
- 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
- enhancer-promoter interactions, long-range chromatin interactions, H3K4me2, CD4+ T cells, chromatin organization, chromosome domains, histone modifications, chromatin accessibility, gene expression regulation
- MeSH terms
- Chromatin, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Promoter Regions, Genetic, Histone-Lysine N-Methyltransferase, Genome, Human
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