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Molecular and Cellular Biology, January 2003, p. 289-305, Vol. 23, No. 1
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.1.289-305.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Drosophila SNR1 (SNF5/INI1) Subunit Directs Essential Developmental Functions of the Brahma Chromatin Remodeling Complex

Daniel R. Marenda, Claudia B. Zraly, Yun Feng,{dagger} Susan Egan,{ddagger} and Andrew K. Dingwall*

Department of Biology, Syracuse University, Syracuse, New York 13244-1270

Received 20 September 2002/ Accepted 26 September 2002

The Drosophila melanogaster Brahma (Brm) complex, a counterpart of the Saccharomyces cerevisiae SWI/SNF ATP-dependent chromatin remodeling complex, is important for proper development by maintaining specific gene expression patterns. The SNR1 subunit is strongly conserved with yeast SNF5 and mammalian INI1 and is required for full activity of the Brm complex. We identified a temperature-sensitive allele of snr1 caused by a single amino acid substitution in the conserved repeat 2 region, implicated in a variety of protein-protein interactions. Genetic analyses of snr1E1 reveal that it functions as an antimorph and that snr1 has critical roles in tissue patterning and growth control. Temperature shifts show that snr1 is continuously required, with essential functions in embryogenesis, pupal stages, and adults. Allele-specific genetic interactions between snr1E1 and mutations in genes encoding other members of the Brm complex suggest that snr1E1 mutant phenotypes result from reduced Brm complex function. Consistent with this view, SNR1E1 is stably associated with other components of the Brm complex at the restrictive temperature. SNR1 can establish direct contacts through the conserved repeat 2 region with the SET domain of the homeotic regulator Trithorax (TRX), and SNR1E1 is partially defective for functional TRX association. As truncating mutations of INI1 are strongly correlated with aggressive cancers, our results support the view that SNR1, and specifically the repeat 2 region, has a critical role in mediating cell growth control functions of the metazoan SWI/SNF complexes.

* Corresponding author. Mailing address: Department of Biology, Syracuse University, 108 College Place, Lyman 422A, Syracuse, NY 13244-1270. Phone: (315) 443-2570. Fax: (315) 443-2156. E-mail: akdingwa{at}syr.edu.

{dagger} Present address: Genome Therapies Inc., Waltham, MA 02453.

{ddagger} Present address: Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210.

Molecular and Cellular Biology, January 2003, p. 289-305, Vol. 23, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.1.289-305.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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