BRD4 is a histone acetyltransferase that evicts nucleosomes from chromatin
| Autor: | Daoud Meerzaman, Anup Dey, Chanelle Case-Borden, Dinah S. Singer, Chih Hao Hsu, Qing-Rong Chen, Anne Gegonne, Ballachanda N. Devaiah, Keiko Ozato |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell Cycle Proteins Thymus Gland Transcription coregulator Article Chromatin remodeling Cell Line Histones Mice 03 medical and health sciences Histone H1 Acetyl Coenzyme A Acetyltransferases Structural Biology Histone methylation Animals Humans Histone code Nucleosome Molecular Biology Histone Acetyltransferases Binding Sites biology Chemistry Nuclear Proteins Acetylation Histone acetyltransferase Molecular biology Chromatin Nucleosomes 030104 developmental biology biology.protein Transcription Factors |
| Zdroj: | Nat Struct Mol Biol |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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