BRD4 is a histone acetyltransferase that evicts nucleosomes from chromatin

Nat Struct Mol Biol. 2016 Jun;23(6):540-8. doi: 10.1038/nsmb.3228. Epub 2016 May 9.


Bromodomain protein 4 (BRD4) is a chromatin-binding protein implicated in cancer and autoimmune diseases that functions as a scaffold for transcription factors at promoters and super-enhancers. Although chromatin decompaction and transcriptional activation of target genes are associated with BRD4 binding, the mechanisms involved are unknown. We report that BRD4 is a histone acetyltransferase (HAT) that acetylates histones H3 and H4 with a pattern distinct from those of other HATs. Both mouse and human BRD4 have intrinsic HAT activity. Importantly, BRD4 acetylates H3 K122, a residue critical for nucleosome stability, thus resulting in nucleosome eviction and chromatin decompaction. Nucleosome clearance by BRD4 occurs genome wide, including at its targets MYC, FOS and AURKB (Aurora B kinase), resulting in increased transcription. These findings suggest a model wherein BRD4 actively links chromatin structure and transcription: it mediates chromatin decompaction by acetylating and evicting nucleosomes at target genes, thereby activating transcription.

MeSH terms

  • Acetyl Coenzyme A / metabolism
  • Acetylation
  • Acetyltransferases / metabolism*
  • Animals
  • Binding Sites
  • Cell Cycle Proteins
  • Cell Line
  • Chromatin / metabolism*
  • Histone Acetyltransferases / metabolism*
  • Histones / metabolism*
  • Humans
  • Mice
  • Nuclear Proteins / metabolism*
  • Nucleosomes / metabolism*
  • Thymus Gland / metabolism
  • Transcription Factors / metabolism*


  • BRD4 protein, human
  • Brd4 protein, mouse
  • Cell Cycle Proteins
  • Chromatin
  • Histones
  • Nuclear Proteins
  • Nucleosomes
  • Transcription Factors
  • Acetyl Coenzyme A
  • Acetyltransferases
  • Histone Acetyltransferases