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

Naturevolume 366pages170174 (1993) | Download Citation

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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 information

Author notes

    • Dirk B. Mendel

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

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

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https://doi.org/10.1038/366170a0

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