H3K4me3 breadth is linked to cell identity and transcriptional consistency

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 fu...

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Bibliographic Details
Published in:Cell Vol. 158; no. 3; p. 673
Main Authors: 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
Format: Journal Article
Language:English
Published: United States 31.07.2014
Subjects:
Animals
Artificial Intelligence
Cells - metabolism
Genomics
Histone Code
Histones - metabolism
Humans
Lysine - metabolism
Methylation
Mice, Inbred C57BL
Neural Stem Cells - metabolism
RNA Polymerase II - metabolism
Transcription, Genetic
ISSN:1097-4172, 1097-4172
Online Access:Get more information
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Summary: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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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2014.06.027