reChIP-seq reveals widespread bivalency of H3K4me3 and H3K27me3 in CD4(+) memory T cells

Nat Commun. 2016 Aug 17:7:12514. doi: 10.1038/ncomms12514.

Abstract

The combinatorial action of co-localizing chromatin modifications and regulators determines chromatin structure and function. However, identifying co-localizing chromatin features in a high-throughput manner remains a technical challenge. Here we describe a novel reChIP-seq approach and tailored bioinformatic analysis tool, normR that allows for the sequential enrichment and detection of co-localizing DNA-associated proteins in an unbiased and genome-wide manner. We illustrate the utility of the reChIP-seq method and normR by identifying H3K4me3 or H3K27me3 bivalently modified nucleosomes in primary human CD4(+) memory T cells. We unravel widespread bivalency at hypomethylated CpG-islands coinciding with inactive promoters of developmental regulators. reChIP-seq additionally uncovered heterogeneous bivalency in the population, which was undetectable by intersecting H3K4me3 and H3K27me3 ChIP-seq tracks. Finally, we provide evidence that bivalency is established and stabilized by an interplay between the genome and epigenome. Our reChIP-seq approach augments conventional ChIP-seq and is broadly applicable to unravel combinatorial modes of action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • CD4-Positive T-Lymphocytes / metabolism*
  • Chromatin Immunoprecipitation / methods*
  • CpG Islands / genetics
  • DNA Methylation / genetics
  • Epigenesis, Genetic
  • Genome, Human
  • Histones / metabolism*
  • Humans
  • Lysine / metabolism*
  • Methylation
  • Models, Genetic
  • Promoter Regions, Genetic
  • Sequence Analysis, DNA
  • Transcription Initiation Site

Substances

  • Histones
  • Lysine