Differential H3K4 methylation identifies developmentally poised hematopoietic genes

Dev Cell. 2008 May;14(5):798-809. doi: 10.1016/j.devcel.2008.04.002.

Abstract

Throughout development, cell fate decisions are converted into epigenetic information that determines cellular identity. Covalent histone modifications are heritable epigenetic marks and are hypothesized to play a central role in this process. In this report, we assess the concordance of histone H3 lysine 4 dimethylation (H3K4me2) and trimethylation (H3K4me3) on a genome-wide scale in erythroid development by analyzing pluripotent, multipotent, and unipotent cell types. Although H3K4me2 and H3K4me3 are concordant at most genes, multipotential hematopoietic cells have a subset of genes that are differentially methylated (H3K4me2+/me3-). These genes are transcriptionally silent, highly enriched in lineage-specific hematopoietic genes, and uniquely susceptible to differentiation-induced H3K4 demethylation. Self-renewing embryonic stem cells, which restrict H3K4 methylation to genes that contain CpG islands (CGIs), lack H3K4me2+/me3- genes. These data reveal distinct epigenetic regulation of CGI and non-CGI genes during development and indicate an interactive relationship between DNA sequence and differential H3K4 methylation in lineage-specific differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Bone Marrow Cells / cytology
  • Cell Differentiation
  • Cell Line
  • Cell Lineage
  • CpG Islands / genetics
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Gene Expression Regulation, Developmental
  • Genes, Developmental*
  • Genome
  • Hematopoietic System / cytology
  • Hematopoietic System / embryology*
  • Hematopoietic System / metabolism*
  • Histones / metabolism*
  • Humans
  • Lysine / metabolism*
  • Methylation
  • Mice
  • Models, Genetic
  • Promoter Regions, Genetic / genetics
  • Transcription Factors / metabolism
  • Transcription Initiation Site
  • Transcription, Genetic

Substances

  • Histones
  • Transcription Factors
  • Lysine