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

Author

Listed:
  • Emma A. Morrison

    (Carver College of Medicine, University of Iowa)

  • Julio C. Sanchez

    (Carver College of Medicine, University of Iowa)

  • Jehnna L. Ronan

    (Program in Cancer Biology, Stanford University School of Medicine)

  • Daniel P. Farrell

    (Carver College of Medicine, University of Iowa
    Present address: Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA)

  • Katayoun Varzavand

    (Carver College of Medicine, University of Iowa)

  • Jenna K. Johnson

    (Carver College of Medicine, University of Iowa
    Present address: Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA)

  • Brian X. Gu

    (Carver College of Medicine, University of Iowa)

  • Gerald R. Crabtree

    (Program in Cancer Biology, Stanford University School of Medicine
    Howard Hughes Medical Institute, Stanford University School of Medicine)

  • Catherine A. Musselman

    (Carver College of Medicine, University of Iowa)

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.

Suggested Citation

  • Emma A. Morrison & Julio C. Sanchez & Jehnna L. Ronan & Daniel P. Farrell & Katayoun Varzavand & Jenna K. Johnson & Brian X. Gu & Gerald R. Crabtree & Catherine A. Musselman, 2017. "DNA binding drives the association of BRG1/hBRM bromodomains with nucleosomes," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16080
    DOI: 10.1038/ncomms16080
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    Cited by:

    1. Dhurjhoti Saha & Solomon Hailu & Arjan Hada & Junwoo Lee & Jie Luo & Jeff A. Ranish & Yuan-chi Lin & Kyle Feola & Jim Persinger & Abhinav Jain & Bin Liu & Yue Lu & Payel Sen & Blaine Bartholomew, 2023. "The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Wilfried Engl & Aliz Kunstar-Thomas & Siyi Chen & Woei Shyuan Ng & Hendrik Sielaff & Ziqing Winston Zhao, 2024. "Single-molecule imaging of SWI/SNF chromatin remodelers reveals bromodomain-mediated and cancer-mutants-specific landscape of multi-modal DNA-binding dynamics," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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