Faculty Collaboration Database

DNA binding drives the association of BRG1/hBRM bromodomains with nucleosomes. Nat Commun 2017 Jul 14;8:16080

Date

07/15/2017

Pubmed ID

28706277

Pubmed Central ID

PMC5519978

DOI

10.1038/ncomms16080

Scopus ID

2-s2.0-85024494914 (requires institutional sign-in at Scopus site)   46 Citations

Abstract

BRG1 and BRM, central components of the BAF (mSWI/SNF) chromatin remodelling complex, are critical in chromatin structure regulation. Here, we show that the human BRM (hBRM) bromodomain (BRD) has moderate specificity for H3K14ac. Surprisingly, we also find that both BRG1 and hBRM BRDs have DNA-binding activity. We demonstrate that the BRDs associate with DNA through a surface basic patch and that the BRD and an adjacent AT-hook make multivalent contacts with DNA, leading to robust affinity and moderate specificity for AT-rich elements. Although we show that the BRDs can bind to both DNA and H3K14ac simultaneously, the histone-binding activity does not contribute substantially to nucleosome targeting in vitro. In addition, we find that neither BRD histone nor DNA binding contribute to the global chromatin affinity of BRG1 in mouse embryonic stem cells. Together, our results suggest that association of the BRG1/hBRM BRD with nucleosomes plays a regulatory rather than targeting role in BAF activity.

Author List

Morrison EA, Sanchez JC, Ronan JL, Farrell DP, Varzavand K, Johnson JK, Gu BX, Crabtree GR, Musselman CA

Author

Emma A. Morrison PhD Assistant Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
DNA
DNA Helicases
Histones
Humans
Mice
Nuclear Proteins
Nucleosomes
Transcription Factors