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Cell. 2014 Jul 31;158(3):673-88. doi: 10.1016/j.cell.2014.06.027.

H3K4me3 breadth is linked to cell identity and transcriptional consistency.

Author information

1
Department of Genetics, Stanford University, Stanford CA 94305, USA; Paul F. Glenn Laboratories for the Biology of Aging, Stanford University, Stanford CA 94305, USA.
2
Department of Genetics, Stanford University, Stanford CA 94305, USA; Cancer Biology Program, Stanford University, Stanford CA 94305, USA.
3
Department of Genetics, Stanford University, Stanford CA 94305, USA.
4
Paul F. Glenn Laboratories for the Biology of Aging, Stanford University, Stanford CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford CA 94305, USA; RR&D REAP, VA Palo Alto Health Care Systems, Palo Alto, CA 94304,USA.
5
Department of Genetics, Stanford University, Stanford CA 94305, USA; Paul F. Glenn Laboratories for the Biology of Aging, Stanford University, Stanford CA 94305, USA; Cancer Biology Program, Stanford University, Stanford CA 94305, USA. Electronic address: anne.brunet@stanford.edu.

Erratum in

  • Cell. 2015 Nov 19;163(5):1281-6.

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.

PMID:
25083876
PMCID:
PMC4137894
DOI:
10.1016/j.cell.2014.06.027
[Indexed for MEDLINE]
Free PMC Article

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