Journal article
The molecular basis of selective DNA binding by the BRG1 AT-hook and bromodomain
Biochimica et biophysica acta. Gene regulatory mechanisms, Vol.1863(8), pp.194566-194566
08/2020
DOI: 10.1016/j.bbagrm.2020.194566
PMID: 32376391
Abstract
The ATP-dependent BAF chromatin remodeling complex plays a critical role in gene regulation by modulating chromatin architecture, and is frequently mutated in cancer. Indeed, subunits of the BAF complex are found to be mutated in >20% of human tumors. The mechanism by which BAF properly navigates chromatin is not fully understood, but is thought to involve a multivalent network of histone and DNA contacts. We previously identified a composite domain in the BRG1 ATPase subunit that is capable of associating with both histones and DNA in a multivalent manner. Mapping the DNA binding pocket revealed that it contains several cancer mutations. Here, we utilize SELEX-seq to investigate the DNA specificity of this composite domain and NMR spectroscopy and molecular modelling to determine the structural basis of DNA binding. Finally, we demonstrate that cancer mutations in this domain alter the mode of DNA association.
•The BRG1 AT-BD binds multivalently to DNA.•The BRG1 AT-BD is selective for AATTAAAT containing sequences.•The BRG1 AT-BD spans the minor and major grooves of DNA.
Details
- Title: Subtitle
- The molecular basis of selective DNA binding by the BRG1 AT-hook and bromodomain
- Creators
- Julio C Sanchez - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesLiyang Zhang - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesStefania Evoli - Department of Physics and The Center for Molecular Study of Condensed Soft Matter, Illinois Institute of Technology, Chicago, IL, United StatesNicholas J Schnicker - Protein & Crystallography Facility, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesMaria Nunez-Hernandez - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesLiping Yu - Department of Biochemistry, Carver College of Medicine NMR Core Facility, University of Iowa, Iowa City, IA 52242, United StatesJeff Wereszczynski - Department of Physics and The Center for Molecular Study of Condensed Soft Matter, Illinois Institute of Technology, Chicago, IL, United StatesMiles A Pufall - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesCatherine A Musselman - Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Biochimica et biophysica acta. Gene regulatory mechanisms, Vol.1863(8), pp.194566-194566
- DOI
- 10.1016/j.bbagrm.2020.194566
- PMID
- 32376391
- NLM abbreviation
- Biochim Biophys Acta Gene Regul Mech
- ISSN
- 1874-9399
- eISSN
- 1876-4320
- Publisher
- Elsevier B.V
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health; DOI: 10.13039/100000001, name: National Science Foundation; DOI: 10.13039/100000054, name: National Cancer Institute
- Language
- English
- Date published
- 08/2020
- Academic Unit
- Molecular Physiology and Biophysics; Biochemistry and Molecular Biology; Chemical and Biochemical Engineering; Medicine Administration
- Record Identifier
- 9984066101402771
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