Identification of H3K4me1-associated proteins at mammalian enhancers

Nat Genet. 2018 Jan;50(1):73-82. doi: 10.1038/s41588-017-0015-6. Epub 2017 Dec 18.


Enhancers act to regulate cell-type-specific gene expression by facilitating the transcription of target genes. In mammalian cells, active or primed enhancers are commonly marked by monomethylation of histone H3 at lysine 4 (H3K4me1) in a cell-type-specific manner. Whether and how this histone modification regulates enhancer-dependent transcription programs in mammals is unclear. In this study, we conducted SILAC mass spectrometry experiments with mononucleosomes and identified multiple H3K4me1-associated proteins, including many involved in chromatin remodeling. We demonstrate that H3K4me1 augments association of the chromatin-remodeling complex BAF to enhancers in vivo and that, in vitro, H3K4me1-marked nucleosomes are more efficiently remodeled by the BAF complex. Crystal structures of the BAF component BAF45C indicate that monomethylation, but not trimethylation, is accommodated by BAF45C's H3K4-binding site. Our results suggest that H3K4me1 has an active role at enhancers by facilitating binding of the BAF complex and possibly other chromatin regulators.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly
  • Enhancer Elements, Genetic*
  • HeLa Cells
  • Histone Code*
  • Histones / chemistry
  • Histones / metabolism*
  • Humans
  • Lysine / metabolism
  • Mice
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Nucleosomes / metabolism
  • Protein Binding


  • Chromatin
  • Histones
  • Nuclear Proteins
  • Nucleosomes
  • Lysine