DNA-binding Factors Shape the Mouse Methylome at Distal Regulatory Regions

Nature. 2011 Dec 14;480(7378):490-5. doi: 10.1038/nature10716.

Abstract

Methylation of cytosines is an essential epigenetic modification in mammalian genomes, yet the rules that govern methylation patterns remain largely elusive. To gain insights into this process, we generated base-pair-resolution mouse methylomes in stem cells and neuronal progenitors. Advanced quantitative analysis identified low-methylated regions (LMRs) with an average methylation of 30%. These represent CpG-poor distal regulatory regions as evidenced by location, DNase I hypersensitivity, presence of enhancer chromatin marks and enhancer activity in reporter assays. LMRs are occupied by DNA-binding factors and their binding is necessary and sufficient to create LMRs. A comparison of neuronal and stem-cell methylomes confirms this dependency, as cell-type-specific LMRs are occupied by cell-type-specific transcription factors. This study provides methylome references for the mouse and shows that DNA-binding factors locally influence DNA methylation, enabling the identification of active regulatory regions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • CpG Islands
  • Cytosine / metabolism*
  • DNA Methylation*
  • DNA-Binding Proteins / metabolism*
  • Embryonic Stem Cells / cytology
  • Epigenomics*
  • Mice
  • Neurons / cytology
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Stem Cells / cytology
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Transcription Factors
  • Cytosine

Associated data

  • GEO/GSE30206