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DNA binding drives the association of BRG1/hBRM bromodomains with nucleosomes

  1. Author:
    Morrison, Emma A.
    Sanchez, Julio C.
    Ronan, Jehnna L.
    Farrell, Daniel P.
    Varzavand, Katayoun
    Johnson, Jenna K.
    Gu, Brian X.
    Crabtree, Gerald R.
    Musselman, Catherine A.
  2. Author Address

    Univ Iowa, Carver Coll Med, Dept Biochem, Iowa City, IA 52242 USA.Stanford Univ, Sch Med, Program Canc Biol, Stanford, CA 94305 USA.Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA.Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.Univ Washington, Dept Biochem, Seattle, WA 98195 USA.NCI, Ctr Canc Res, Frederick, MD 21702 USA.
    1. Year: 2017
    2. Date: Jul 14
  1. Journal: NATURE COMMUNICATIONS
  2. NATURE PUBLISHING GROUP,
    1. 8
  3. Type of Article: Article
  4. Article Number: 16080
  5. ISSN: 2041-1723
  1. 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.

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External Sources

  1. DOI: 10.1038/ncomms16080
  2. WOS: 000405465500001

Library Notes

  1. Fiscal Year: FY2016-2017
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