Architectural DNA binding by a high-mobility-group/kinesin-like subunit in mammalian SWI/SNF-related complexes
- Weidong Wang*,†,
- Tianhuai Chi†,‡,
- Yutong Xue†,‡,
- Sharleen Zhou‡,§,
- Ann Kuo†,‡, and
- Gerald R. Crabtree†,¶
- †Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University, Stanford, CA 94305-5323; and §Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720-3204
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Contributed by Gerald R. Crabtree
Abstract
The SWI/SNF complex in yeast and Drosophila is thought to facilitate transcriptional activation of specific genes by antagonizing chromatin-mediated transcriptional repression. The mechanism by which it is targeted to specific genes is poorly understood and may involve direct DNA binding and/or interactions with specific or general transcription factors. We have previously purified a mammalian complex by using antibodies against BRG1, a human homologue of SWI2/SNF2. This complex is likely functionally related to the yeast SWI/SNF complex because all five subunits identified so far (referred to as BAFs, for BRG1-associated factors) are homologues of the yeast SWI/SNF subunits. However, we now describe the cloning of the 57-kDa subunit (BAF57), which is present only in higher eukaryotes but not in yeast. BAF57 is shared by all mammalian complexes and contains a high-mobility-group (HMG) domain adjacent to a kinesin-like region. Both recombinant BAF57 and the whole complex bind four-way junction (4WJ) DNA, which is thought to mimic the topology of DNA as it enters or exits the nucleosome. Surprisingly, complexes with mutations in the HMG domain of BAF57 can still bind 4WJ DNA and mediate ATP-dependent nucleosome disruption. Our work describes the first DNA binding subunit for SWI/SNF-like complexes and suggest that the mechanism by which mammalian and Drosophila SWI/SNF-like complexes interact with chromatin may involve recognition of higher-order chromatin structure by two or more DNA binding domains.
Footnotes
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↵ * Present address: Laboratory of Genetics, National Institute on Aging, National Institute of Health, Gerontology Research Center, 4940 Eastern Avenue, Baltimore, MD 21224.
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↵ ‡ T.C., Y.X., S.Z., and A.K. made equal contributions to this work.
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↵ ¶ To whom reprint requests should be addressed. e-mail: hf.grc{at}forsythe.stanford.edu.
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This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected on April 29, 1997.
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Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF035262 and AF035263 for human and murine BAF57, respectively).
- ABBREVIATIONS:
- BAF,
- BRG1-associated factor;
- HMG,
- high mobility group;
- 4WJ,
- four-way junction;
- EST,
- expressed sequence tag;
- HA,
- hemagglutinin;
- NCBI,
- National Center for Biotechnology Information
- Copyright © 1998, The National Academy of Sciences
