H3K4me3 breadth is linked to cell identity and transcriptional consistency
Open accessAbstract
Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to mark the transcription start sites of active genes. Here, we show that H3K4me3 domains that spread more broadly over genes in a given cell type preferentially mark genes that are essential for the identity and function of that cell type. Using the broadest H3K4me3 domains as a discovery tool in neural progenitor cells, we identify novel regulators of these cells. Machine learning models reveal that the broadest H3K4me3 domains represent a distinct entity, characterized by increased marks of elongation. The broadest H3K4me3 domains also have more paused polymerase at their promoters, suggesting a unique transcriptional output. Indeed, genes marked by the broadest H3K4me3 domains exhibit enhanced transcriptional consistency and [corrected] increased transcriptional levels, and perturbation of H3K4me3 breadth leads to changes in transcriptional consistency. Thus, H3K4me3 breadth contains information that could ensure transcriptional precision at key cell identity/function genes.
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H3K4me3 domains vary in breadth in locus- and cell-type-specific manner.
“Interestingly, H3K4me3 domains vary in breadth in a locus- and cell-type-specific manner (Benayoun et al., 2014; Chen et al., 2015), and these differences could provide clues about the context-dependent roles of this mark during aging.”
From The Aging Epigenome (2016) · cites this paper as Benayoun et al., 2014
The breadth of H3K4me3 has been linked to cell identity, gene expression and transcriptional consistency across cell types.
“The breadth of the H3K4me3 mark has been previously linked to cell identity, gene expression and transcriptional consistency across a variety of cell types30.”
From Single-cell CUT&Tag profiles histone modifications and transcription factors in complex tissues (2021) · cites this paper as [30]
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Retracted
- Authors
- Benayoun, B. A., Pollina, E. A., Ucar, D., Mahmoudi, S., Karra, K., Wong, E. D., Devarajan, K., Daugherty, A. C., Kundaje, A. B., Mancini, E., Hitz, B. C., Gupta, R., Rando, T. A., Baker, J. C., Snyder, M. P., Cherry, J. M., & Brunet, A.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- VA Palo Alto Health Care System (US)
- Corresponding author
- Brunet, Anne
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 158
- Issue
- 3
- Pages
- 673-688
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4137894
- OpenAlex
- W1984173288
- Cited by
- 536
- References
- 105
- Citations by year
- 2026: 28 · 2025: 53 · 2024: 52 · 2023: 50 · 2022: 41 · 2021: 57 · 2020: 40 · 2019: 44 · 2018: 32 · 2017: 51 · 2016: 47 · 2015: 38 · 2014: 3
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Update notices
- erratum (2015-11-19)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institute on Aging (F31AG043232, DP1AG044848, P01AG036695)
- National Cancer Institute (T32CA009302)
- National Institute of General Medical Sciences (P01GM099130, R01GM103787, T32GM007790)
- 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
- H3K4me3, histone trimethylation, chromatin modification, transcription start sites, cell identity, neural progenitor cells, gene expression regulation, RNA polymerase II elongation, cell type-specific genes, machine learning
- MeSH terms
- Animals, Artificial Intelligence, Cells, Histones, Humans, Lysine, Methylation, Mice, Inbred C57BL, RNA Polymerase II, Transcription, Genetic, Genomics, Histone Code, Neural Stem Cells
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