Research Article

Structure of nucleosome-bound human BAF complex

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Science  21 Feb 2020:
Vol. 367, Issue 6480, pp. 875-881
DOI: 10.1126/science.aaz9761

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Architecture of human BAF complex

The SWI/SNF family chromatin remodelers regulate chromatin and transcription. The protein complexes BAF and PBAF are mammalian SWI/SNF remodelers that play essential functions in diverse developmental and physiological processes. He et al. determined the structure of the human BAF complex, which contains three modules that bind the nucleosome on the top, bottom, and side, making this nucleosome-recognition pattern distinct from other chromatin remodelers. Mutations in BAF that are frequently associated with human cancer cluster into a nucleosome-interacting region. This structure provides a framework for understanding the BAF-mediated chromatin remodeling mechanism and its dysregulation in cancer.

Science, this issue p. 875

Abstract

Mammalian SWI/SNF family chromatin remodelers, BRG1/BRM-associated factor (BAF) and polybromo-associated BAF (PBAF), regulate chromatin structure and transcription, and their mutations are linked to cancers. The 3.7-angstrom-resolution cryo–electron microscopy structure of human BAF bound to the nucleosome reveals that the nucleosome is sandwiched by the base and the adenosine triphosphatase (ATPase) modules, which are bridged by the actin-related protein (ARP) module. The ATPase motor is positioned proximal to nucleosomal DNA and, upon ATP hydrolysis, engages with and pumps DNA along the nucleosome. The C-terminal α helix of SMARCB1, enriched in positively charged residues frequently mutated in cancers, mediates interactions with an acidic patch of the nucleosome. AT-rich interactive domain-containing protein 1A (ARID1A) and the SWI/SNF complex subunit SMARCC serve as a structural core and scaffold in the base module organization, respectively. Our study provides structural insights into subunit organization and nucleosome recognition of human BAF complex.

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