2026-09-14 ペンシルベニア州立大学（Penn State）
＜関連情報＞
- https://www.psu.edu/news/research/story/cancer-linked-protein-binds-chromosome-unexpected-way-study-finds
- https://www.cell.com/molecular-cell/abstract/S1097-2765(26)00498-3
BRD4はヒストンとDNAの両方との相互作用を介してヌクレオソームに結合する BRD4 binds the nucleosome via both histone and DNA interactions
Jiang Zhu ∙ Erik M. Leith ∙ Erin N. O’Donnell ∙ … ∙ Cheng-Ming Chiang ∙ Jean-Paul Armache ∙ Song Tan
Molecular Cell Published: August 6, 2026
DOI:https://doi.org/10.1016/j.molcel.2026.07.012
Highlights
- How the BRD4 first bromodomain binds to acetylated nucleosomes is revealed by cryo-EM
- BRD4 BD1 presents the histone tail for potential interactions with other proteins
- BRD4-S binds with high affinity to both acetylated and unacetylated nucleosomes
- Histone H4 acetylation influences the conformation of the BRD4-S/nucleosome complex
Summary
BRD4, a bromodomain and extraterminal (BET) family transcriptional regulator, is believed to be recruited to chromatin via interactions between its tandem bromodomains (BD1 and BD2) and acetylated histone tails. Although extensive studies have explained how individual BRD4 bromodomains bind to acetylated peptides and how BET inhibitors interfere with such interactions, equivalent studies of the full-length BRD4 protein with the nucleosome have been lacking. Our cryo-electron microscopy (cryo-EM) structure of the BRD4 short (BRD4-S) isoform bound to a nucleosome diacetylated on histone H4 shows how BRD4 BD1 engages both the H4 tail and nucleosomal DNA. Unlike other chromatin reader domain/nucleosome structures, BRD4 BD1 presents the acetylated histone tail for potential interactions with additional chromatin proteins. Unexpectedly, our biochemical studies indicate that BRD4 uses basic regions outside of the bromodomains to bind nucleosomes tightly even in the absence of histone acetylation. Our results further show that histone H4 acetylation influences the conformation of the BRD4/nucleosome complex.
