Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells

Nature. 2016 Feb 4;530(7588):113-6. doi: 10.1038/nature16505. Epub 2016 Jan 27.


ATP-dependent chromatin remodellers allow access to DNA for transcription factors and the general transcription machinery, but whether mammalian chromatin remodellers target specific nucleosomes to regulate transcription is unclear. Here we present genome-wide remodeller-nucleosome interaction profiles for the chromatin remodellers Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind one or both full nucleosomes that flank micrococcal nuclease (MNase)-defined nucleosome-free promoter regions (NFRs), where they separate divergent transcription. Surprisingly, large CpG-rich NFRs that extend downstream of annotated transcriptional start sites are nevertheless bound by non-nucleosomal or subnucleosomal histone variants (H3.3 and H2A.Z) and marked by H3K4me3 and H3K27ac modifications. RNA polymerase II therefore navigates hundreds of base pairs of altered chromatin in the sense direction before encountering an MNase-resistant nucleosome at the 3' end of the NFR. Transcriptome analysis after remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. Whereas at active genes individual remodellers have either positive or negative roles via altering nucleosome stability, at polycomb-enriched bivalent genes the same remodellers act in an opposite manner. These findings indicate that remodellers target specific nucleosomes at the edge of NFRs, where they regulate ES cell transcriptional programs.

Publication types

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

MeSH terms

  • Animals
  • Chromatin Assembly and Disassembly*
  • DNA Helicases / metabolism
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation*
  • Genome / genetics*
  • Histones / metabolism
  • Mice
  • Micrococcal Nuclease / metabolism
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism*
  • Nuclear Proteins / metabolism
  • Nucleosomes / genetics*
  • Nucleosomes / metabolism*
  • Promoter Regions, Genetic / genetics
  • RNA Polymerase II / metabolism
  • Substrate Specificity
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism
  • Transcription Initiation Site


  • Chd1 protein, mouse
  • Chd2 protein, mouse
  • DNA-Binding Proteins
  • Ep400 protein, mouse
  • Histones
  • Nuclear Proteins
  • Nucleosomes
  • Trans-Activators
  • Transcription Factors
  • duplin protein, mouse
  • RNA Polymerase II
  • Micrococcal Nuclease
  • Smarca4 protein, mouse
  • Mi-2beta protein, mouse
  • DNA Helicases
  • Chd6 protein, mouse
  • Chd9 protein, mouse

Associated data

  • GEO/GSE64819
  • GEO/GSE64825