| First Author | Devaiah BN | Year | 2016 |
| Journal | Nat Struct Mol Biol | Volume | 23 |
| Issue | 6 | Pages | 540-8 |
| PubMed ID | 27159561 | Mgi Jnum | J:331732 |
| Mgi Id | MGI:6741016 | Doi | 10.1038/nsmb.3228 |
| Citation | Devaiah BN, et al. (2016) BRD4 is a histone acetyltransferase that evicts nucleosomes from chromatin. Nat Struct Mol Biol 23(6):540-8 |
| abstractText | 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. |
