DNA methylation status predicts cell type‐specific enhancer activity
Open accessAbstract
Cell-selective glucocorticoid receptor (GR) binding to distal regulatory elements is associated with cell type-specific regions of locally accessible chromatin. These regions can either pre-exist in chromatin (pre-programmed) or be induced by the receptor (de novo). Mechanisms that create and maintain these sites are not well understood. We observe a global enrichment of CpG density for pre-programmed elements, and implicate their demethylated state in the maintenance of open chromatin in a tissue-specific manner. In contrast, sites that are actively opened by GR (de novo) are characterized by low CpG density, and form a unique class of enhancers devoid of suppressive effect of agglomerated methyl-cytosines. Furthermore, treatment with glucocorticoids induces rapid changes in methylation levels at selected CpGs within de novo sites. Finally, we identify GR-binding elements with CpGs at critical positions, and show that methylation can affect GR-DNA interactions in vitro. The findings present a unique link between tissue-specific chromatin accessibility, DNA methylation and transcription factor binding and show that DNA methylation can be an integral component of gene regulation by nuclear receptors.
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The presence of DNA methylation negatively correlates with enhancer activity and alters the ability of tissue-specific DNA-binding proteins to bind their target sites.
“In addition, the presence of DNA methylation has been shown to negatively correlate with enhancer activity41 and alters the ability of tissue-specific DNA-binding proteins to bind their target sites.34”
From Vitamin C-induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia (2018) · cites this paper as [41]
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- Authors
- Wiench, M., John, S., Baek, S., Johnson, T. A., Sung, M., Escobar, T., Simmons, C. A., Pearce, K. H., Biddie, S. C., Sabo, P. J., Thurman, R. E., Stamatoyannopoulos, J. A., & Hager, G. L.
- Affiliations
- National Institutes of Health (US)
- GlaxoSmithKline (United States) (US)
- University of Washington (US)
- Corresponding author
- Hager, Gordon L
- ORCID
- Venue
- The EMBO Journal
- Published
- 2011-06-24
- Volume
- 30
- Issue
- 15
- Pages
- 3028-3039
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC3160184
- OpenAlex
- W1983347147
- Cited by
- 245
- References
- 64
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 12 · 2023: 8 · 2022: 19 · 2021: 22 · 2020: 7 · 2019: 13 · 2018: 9 · 2017: 15 · 2016: 20 · 2015: 24 · 2014: 31 · 2013: 28 · 2012: 24
- FWCI
- 11.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- 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
- Keywords
- DNA methylation, glucocorticoid receptor, enhancer activity, CpG density, open chromatin, nuclear receptor binding, transcription factor-DNA interaction, glucocorticoid therapy, tissue-specific gene regulation
- MeSH terms
- Animals, Cell Line, Chromatin, DNA, Enhancer Elements, Genetic, Protein Binding, Receptors, Glucocorticoid, DNA Methylation, Mice
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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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