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BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription

Nature volume 366, pages 170–174 (1993)Cite this article

Abstract

SEQUENCE-SPECIFIC DNA binding activators of gene transcription may be assisted by SWI2(SNF2)1,2, which contains a DNA-depen-dent ATPase domain3. We have isolated a human complementary DNA encoding a 205K nuclear protein, BRG1, that contains extensive homology to SWI2 and Drosophila brahma4,5. We report here that a SWI2/BRG1 chimaera with the DNA-dependent ATPase domain replaced by corresponding human sequence restored normal mitotic growth and capacity for transcriptional activation to swi2& minus; yeast cells. Point mutation of the conserved ATP binding site lysine abolished this complementation. This mutation in SW12 exerted a dominant negative effect on transcription in yeast. A lysine to arginine substitution at the corresponding residue of BRG1 also generated a transcriptional dominant negative in human cells. BRG1 is exclusively nuclear and present in a high Mr complex of about 2 & times; 106. These results show that the SWI2 family DNA-dependent ATPase domain has functional con-servation between yeast and humans and suggest that a SWI/SNF protein complex is required for the activation of selective mammalian genes.

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Author notes

  1. Dirk B. Mendel

    Present address: Gilead Sciences, 353 Lakeside Drive, Foster City, California, 94040, USA

Authors and Affiliations

  1. Howard Hughes Medical Institute, Center for Molecular and Genetic Medicine, Stanford University, Stanford, California, 94305, USA

    Paul A. Khavari, Dirk B. Mendel & Gerald R. Crabtree

  2. Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester, Massachusetts, 01650, USA

    Craig L. Peterson

  3. Department of Biology, University of California, Santa Cruz, California, 95064, USA

    John W. Tamkun

Authors
  1. Paul A. Khavari
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  2. Craig L. Peterson
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  3. John W. Tamkun
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  4. Dirk B. Mendel
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  5. Gerald R. Crabtree
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Khavari, P., Peterson, C., Tamkun, J. et al. BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription. Nature 366, 170–174 (1993). https://doi.org/10.1038/366170a0

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