H3K4me3 breadth is linked to cell identity and transcriptional consistency

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

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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 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*

Substances

  • Histones
  • RNA Polymerase II
  • Lysine