Quantitative Interaction Proteomics and Genome-Wide Profiling of Epigenetic Histone Marks and Their Readers

Cell. 2010 Sep 17;142(6):967-80. doi: 10.1016/j.cell.2010.08.020.

Abstract

Trimethyl-lysine (me3) modifications on histones are the most stable epigenetic marks and they control chromatin-mediated regulation of gene expression. Here, we determine proteins that bind these marks by high-accuracy, quantitative mass spectrometry. These chromatin "readers" are assigned to complexes by interaction proteomics of full-length BAC-GFP-tagged proteins. ChIP-Seq profiling identifies their genomic binding sites, revealing functional properties. Among the main findings, the human SAGA complex binds to H3K4me3 via a double Tudor-domain in the C terminus of Sgf29, and the PWWP domain is identified as a putative H3K36me3 binding motif. The ORC complex, including LRWD1, binds to the three most prominent transcriptional repressive lysine methylation sites. Our data reveal a highly adapted interplay between chromatin marks and their associated protein complexes. Reading specific trimethyl-lysine sites by specialized complexes appears to be a widespread mechanism to mediate gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / metabolism*
  • Epigenesis, Genetic*
  • Gene Expression Regulation
  • Genome-Wide Association Study
  • HeLa Cells
  • Histone Acetyltransferases / metabolism
  • Histone Code*
  • Humans
  • Lysine / metabolism
  • Mass Spectrometry
  • Methylation
  • Proteomics / methods

Substances

  • Chromatin
  • Histone Acetyltransferases
  • Lysine