Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells

PLoS Genet. 2011 Jun;7(6):e1002154. doi: 10.1371/journal.pgen.1002154. Epub 2011 Jun 23.

Abstract

Covalent modification of DNA distinguishes cellular identities and is crucial for regulating the pluripotency and differentiation of embryonic stem (ES) cells. The recent demonstration that 5-methylcytosine (5-mC) may be further modified to 5-hydroxymethylcytosine (5-hmC) in ES cells has revealed a novel regulatory paradigm to modulate the epigenetic landscape of pluripotency. To understand the role of 5-hmC in the epigenomic landscape of pluripotent cells, here we profile the genome-wide 5-hmC distribution and correlate it with the genomic profiles of 11 diverse histone modifications and six transcription factors in human ES cells. By integrating genomic 5-hmC signals with maps of histone enrichment, we link particular pluripotency-associated chromatin contexts with 5-hmC. Intriguingly, through additional correlations with defined chromatin signatures at promoter and enhancer subtypes, we show distinct enrichment of 5-hmC at enhancers marked with H3K4me1 and H3K27ac. These results suggest potential role(s) for 5-hmC in the regulation of specific promoters and enhancers. In addition, our results provide a detailed epigenomic map of 5-hmC from which to pursue future functional studies on the diverse regulatory roles associated with 5-hmC.

Publication types

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

MeSH terms

  • 5-Methylcytosine / metabolism
  • Binding Sites
  • Cell Line
  • Chromosome Mapping
  • Cytosine / analogs & derivatives*
  • Cytosine / metabolism
  • DNA Methylation
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Epigenomics*
  • Gene Expression Regulation
  • Gene Library
  • Genome, Human*
  • Heterochromatin / chemistry
  • Histones / metabolism
  • Humans
  • Immunoblotting
  • Metaphase
  • Promoter Regions, Genetic
  • Sequence Alignment
  • Transcription Factors / metabolism

Substances

  • Heterochromatin
  • Histones
  • Transcription Factors
  • 5-hydroxymethylcytosine
  • 5-Methylcytosine
  • Cytosine