Cited by 551Genomics and Chromatin DynamicsEpigenetics and DNA MethylationChromatin Remodeling and Cancer

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H3K4me3 Breadth Is Linked to Cell Identity and Transcriptional Consistency

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Benayoun, Bérénice A., Pollina, Elizabeth A., Ucar, Duygu, Mahmoudi, Salah, Karra, Kalpana, Wong, Edith D., Devarajan, Keerthana, Daugherty, Aaron C., Kundaje, Anshul B., Mancini, Elena, Hitz, Benjamin C., Gupta, Rakhi, Rando, Thomas A., Baker, Julie C., Snyder, Michael P., Cherry, J. Michael, Brunet, Anne·2014·Cell

DOI 10.1016/j.cell.2014.06.027PMC PMC4137894

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Abstract

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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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: Benayoun, Bérénice A.
Pollina, Elizabeth A.
Ucar, Duygu
Karra, Kalpana
Wong, Edith D.
Devarajan, Keerthana
Kundaje, Anshul B.
Hitz, Benjamin C.
Rando, Thomas A.
Baker, Julie C.
Snyder, Michael P.
Cherry, J. Michael
Brunet, Anne
Venue: Cell
Publisher: Elsevier BV
Published: 2014-07
Volume: 158
Issue: 3
Pages: 673-688
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2014.06.027
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 395 d)
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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H3K4me3 Breadth Is Linked to Cell Identity and Transcriptional Consistency

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