The double bromodomain proteins Brd2 and Brd3 couple histone acetylation to transcription

Mol Cell. 2008 Apr 11;30(1):51-60. doi: 10.1016/j.molcel.2008.01.018.

Abstract

Posttranslational histone modifications are crucial for the modulation of chromatin structure and regulation of transcription. Bromodomains present in many chromatin-associated proteins recognize acetylated lysines in the unstructured N-terminal regions of histones. Here, we report that the double bromodomain proteins Brd2 and Brd3 associate preferentially in vivo with hyperacetylated chromatin along the entire lengths of transcribed genes. Brd2- and Brd3-associated chromatin is significantly enriched in H4K5, H4K12, and H3K14 acetylation and contains relatively little dimethylated H3K9. Both Brd2 and Brd3 allowed RNA polymerase II to transcribe through nucleosomes in a defined transcription system. Such activity depended on specific histone H4 modifications known to be recognized by the Brd proteins. We also demonstrate that Brd2 has intrinsic histone chaperone activity and is required for transcription of the cyclin D1 gene in vivo. These data identify proteins that render nucleosomes marked by acetylation permissive to the passage of elongating RNA polymerase II.

Publication types

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

MeSH terms

  • Acetylation
  • Chromatin / metabolism
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Gene Expression Regulation*
  • Histones / metabolism*
  • Humans
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Protein Processing, Post-Translational*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • RNA Polymerase II / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Transcription Factors
  • Transcription, Genetic*

Substances

  • BRD2 protein, human
  • BRD3 protein, human
  • Chromatin
  • Histones
  • Molecular Chaperones
  • RNA-Binding Proteins
  • Transcription Factors
  • Cyclin D1
  • Protein-Serine-Threonine Kinases
  • RNA Polymerase II