Paul A. Khavari, MD, PhD

Publication Details

  • BRG1 CONTAINS A CONSERVED DOMAIN OF THE SWI2/SNF2 FAMILY NECESSARY FOR NORMAL MITOTIC GROWTH AND TRANSCRIPTION NATURE Khavari, P. A., Peterson, C. L., Tamkun, J. W., Mendel, D. B., Crabtree, G. R. 1993; 366 (6451): 170-174


    Sequence-specific DNA binding activators of gene transcription may be assisted by SWI2 (SNF2), which contains a DNA-dependent ATPase domain. We have isolated a human complementary DNA encoding a 205K nuclear protein, BRG1, that contains extensive homology to SWI2 and Drosophila brahma. We report here that a SWI2/BRG1 chimera with the DNA-dependent ATPase domain replaced by corresponding human sequence restored normal mitotic growth and capacity for transcriptional activation to swi2- yeast cells. Point mutation of the conserved ATP binding site lysine abolished this complementation. This mutation in SWI2 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 M(r) complex of about 2 x 10(6). These results show that the SWI2 family DNA-dependent ATPase domain has functional conservation between yeast and humans and suggest that a SWI/SNF protein complex is required for the activation of selective mammalian genes.

    View details for Web of Science ID A1993MG21600061

    View details for PubMedID 8232556

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