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Histone H3K27ac separates active from poised enhancers and predicts developmental state
Open accessAbstract
Developmental programs are controlled by transcription factors and chromatin regulators, which maintain specific gene expression programs through epigenetic modification of the genome. These regulatory events at enhancers contribute to the specific gene expression programs that determine cell state and the potential for differentiation into new cell types. Although enhancer elements are known to be associated with certain histone modifications and transcription factors, the relationship of these modifications to gene expression and developmental state has not been clearly defined. Here we interrogate the epigenetic landscape of enhancer elements in embryonic stem cells and several adult tissues in the mouse. We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements containing H3K4me1 alone. This indicates that the amount of actively used enhancers is lower than previously anticipated. Furthermore, poised enhancer networks provide clues to unrealized developmental programs. Finally, we show that enhancers are reset during nuclear reprogramming.
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“providing support for the upstream region being an enhancer element that becomes active upon TLR-4 activation (Creyghton et al., 2010).”
From TET2 Regulates the Neuroinflammatory Response in Microglia (2019) · cites this paper as Creyghton et al., 2010
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“Currently mono-methylation of histone H3 lysine 4 (H3K4me1), associated with the binding of Trithorax/MLL complexes, is taken to be the hallmark of both ‘primed’ and active enhancers, whilst active enhancers additionally tend to associate with the acetylation of histone H3 lysine 27 (H3K27ac) [133–137].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [133]
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“In the cerebral cortex, rs1057233- and rs78245530-harboring regions exhibited enhancer activity (indicated by the low H3K4me3 signal and high H3K27ac signal [45]) (Fig. 2d).”
From Association of SPI1 haplotypes with altered SPI1 gene expression and Alzheimer’s disease risk (2022) · cites this paper as [45]
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“Monomethylation on H3K4 (H3K4me1) in combination with acetylation of H3 at K27 (H3K27ac) designates the active enhancer state33 while H3K4me1 alone, or with trimethylation of H3K27 (H3K27me3), defines a primed or repressed enhancer, respectively30.”
From HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements (2024) · cites this paper as [33]
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“Assisted loading events are coupled with increases in enhancer activity as measured by DNase hypersensitivity or H3K27 acetylation (H3K27ac), two well-established markers for active enhancers38–40.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [39]
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Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368
Self-citationMaster Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes
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Self-citationSuper-enhancers in the control of cell identity and disease
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Self-citationSelective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers
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Metadata
- Authors
- Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., Boyer, L. A., Young, R. A., & Jaenisch, R.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Jaenisch, Rudolf
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-11-24
- Volume
- 107
- Issue
- 50
- Pages
- 21931-21936
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3003124
- OpenAlex
- W1981030303
- Cited by
- 4,302
- References
- 9
- Citations by year
- 2026: 228 · 2025: 286 · 2024: 349 · 2023: 365 · 2022: 345 · 2021: 362 · 2020: 346 · 2019: 315 · 2018: 292 · 2017: 267 · 2016: 261 · 2015: 242 · 2014: 239 · 2013: 220 · 2012: 124
- FWCI
- 51.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institutes of Health (2r01ca084198-10)
- U.S. Public Health Service (5-RO1-HDO45022)
- National Human Genome Research Institute (HG002668, R01HG002668)
- National Cancer Institute (R01-CA084198, R01CA087869, 5-RO1-CA87869, P01CA042063, R37CA084198, P30CA014051, P30-CA-14051, P01 CA 42063)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37HD045022)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- enhancer activity, poised enhancers, H3K4me1, developmental state, embryonic stem cells, nuclear reprogramming, cell differentiation, chromatin regulation, mouse tissues
- MeSH terms
- Acetylation, Animals, Cell Differentiation, Cell Line, Enhancer Elements, Genetic, Histones, Mice, Inbred C57BL, Gene Expression Regulation, Developmental, Mice
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