title: BRD4 is a histone acetyltransferase that evicts nucleosomes from chromatin.
abstract: 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.
authors.affiliation: Experimental Immunology Branch, NCI, NIH, Bethesda, Maryland, USA.
authors.forename: Ballachanda N
authors.initials: BN
authors.lastname: Devaiah
authors.affiliation: Experimental Immunology Branch, NCI, NIH, Bethesda, Maryland, USA.
authors.forename: Chanelle
authors.initials: C
authors.lastname: Case-Borden
authors.affiliation: Experimental Immunology Branch, NCI, NIH, Bethesda, Maryland, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Gegonne
authors.affiliation: Center for Biomedical Informatics and Information Technology, NCI, NIH, Bethesda, Maryland, USA.
authors.forename: Chih Hao
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Center for Biomedical Informatics and Information Technology, NCI, NIH, Bethesda, Maryland, USA.
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Center for Biomedical Informatics and Information Technology, NCI, NIH, Bethesda, Maryland, USA.
authors.forename: Daoud
authors.initials: D
authors.lastname: Meerzaman
authors.affiliation: Laboratory of Molecular Growth Regulation, NICHD, NIH, Bethesda, Maryland, USA.
authors.forename: Anup
authors.initials: A
authors.lastname: Dey
authors.affiliation: Laboratory of Molecular Growth Regulation, NICHD, NIH, Bethesda, Maryland, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ozato
authors.affiliation: Experimental Immunology Branch, NCI, NIH, Bethesda, Maryland, USA.
authors.forename: Dinah S
authors.initials: DS
authors.lastname: Singer
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
chemical_list: D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D002843:Chromatin; D051548:Histone Acetyltransferases; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C486694:Brd4 protein, mouse