Skip to main content
SpringerLink
Log in

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

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Peterson, C. L. & Herskowitz, I. J. Cell 68, 573–583 (1992).

    Article  CAS  Google Scholar 

  2. Yoshinaga, S. K., Peterson, C. L., Herskowitz, I. & Yamamoto, K. R. Science 258, 1598–1604 (1992).

    Article  ADS  CAS  Google Scholar 

  3. Laurent, B. C., Treich, I. Carlson, M. Genes Dev. 7, 583–591 (1993).

    Article  CAS  Google Scholar 

  4. Kennison, J. A. & Tamkun, J. W. Proc. natn. Acad. Sci. U.S.A. 85, 8136–8140 (1988).

    Article  ADS  CAS  Google Scholar 

  5. Tamkun, J. W. et al. Cell 68, 561–572 (1992).

    Article  CAS  Google Scholar 

  6. Gill, G. & Tjian, R. Curr. Opin. Genet. Dev. 2, 236–242 (1992).

    Article  CAS  Google Scholar 

  7. Zawel, L. & Reinberg, D. Curr. Opin. Cell Biol. 4, 488–495 (1992).

    Article  CAS  Google Scholar 

  8. Stern, M., Jensen, R. & Herskowitz, I. J. Molec. Biol. 178, 853–868 (1984).

    Article  CAS  Google Scholar 

  9. Neigeborn, L. & Carlson, M. Genetics 108, 845–858 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Winston, F. & Carlson, M. Trends Genet. 8, 387–391 (1992).

    Article  CAS  Google Scholar 

  11. Laurent, B. C. & Carlson, M. Genes Dev. 6, 1707–1715 (1992).

    Article  CAS  Google Scholar 

  12. Peterson, C. L., Kruger, W. & Herskowitz, I. Cell 64, 1135–1143 (1991).

    Article  CAS  Google Scholar 

  13. Hirschhorn, J. N., Brown, S. A., Clark, C. & Winston, F. Genes Dev. 6, 2288–2298 (1992).

    Article  CAS  Google Scholar 

  14. Laurent, B. C., Yang, X. & Carlson, M. Molec. cell. Biol. 12, 1893–1902 (1992).

    Article  CAS  Google Scholar 

  15. Davis, J. L., Kunisawa, R., Thorner, J. Molec. cell. Biol. 12, 1879–1892 (1992).

    Article  CAS  Google Scholar 

  16. Henikoff, S. Trends biochem. Sci. 18, 291–292 (1993).

    Article  CAS  Google Scholar 

  17. Gorbalenya, A. E. et al. Nucleic Acids Res. 17, 4713–4730 (1989).

    Article  CAS  Google Scholar 

  18. Travers, A. A. Cell 69, 573–575 (1992).

    Article  CAS  Google Scholar 

  19. Troelstra, C. et al. Cell 71, 939–953 (1992).

    Article  CAS  Google Scholar 

  20. Okabe, I. et al. Nucleic Acids Res. 20, 4649–4655 (1992).

    Article  CAS  Google Scholar 

  21. Haynes, S. R. et al. Nucleic Acids Res. 20, 2603–2604 (1992).

    Article  ADS  CAS  Google Scholar 

  22. Haynes, S. R., Mozer, B. A., Bhatia-Dey, N. & Dawid, I. B. Devl Biol. 134, 246–257 (1989).

    Article  CAS  Google Scholar 

  23. Georgakopoulos, T. & Thireos, G. EMBO J. 11, 4145–4152 (1992).

    Article  CAS  Google Scholar 

  24. Hisatake, K. et al. Nature 362, 179–181 (1993).

    Article  ADS  CAS  Google Scholar 

  25. Sung, P., Higgins, D., Prakash, L. & Prakash, S. EMBO J. 7, 3263–3269 (1988).

    Article  CAS  Google Scholar 

  26. Pearson, W. R. Meth. Enzym. 183, 63–98 (1990).

    Article  CAS  Google Scholar 

  27. Flanagan, W. M., Corthesy, B., Bram, R. J. & Crabtree, G. R. Nature 352, 803–807 (1991).

    Article  ADS  CAS  Google Scholar 

  28. Mendel, D. B., et al. Science 254, 1762–1767 (1991).

    Article  ADS  CAS  Google Scholar 

  29. Northrop, J. P., Ullman, K. S. & Crabtree, G. R. J. biol. Chem. 268, 2917–2923 (1993).

    CAS  PubMed  Google Scholar 

  30. Ullman, K. S., Northrop, J. P., Admon, A. & Crabtree, G. R. Genes Dev. 7, 188–196 (1993).

    Article  CAS  Google Scholar 

  31. Mizushima, S. & Nagata, S. Nucleic Acids Res. 18, 5322 (1990).

    Article  CAS  Google Scholar 

Download references

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Craig L. Peterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John W. Tamkun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dirk B. Mendel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gerald R. Crabtree
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

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

  • Springer Nature Limited

This article is cited by

Search

Navigation