title: The Drosophila SNR1 (SNF5/INI1) subunit directs essential developmental functions of the Brahma chromatin remodeling complex.
abstract: 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 snr1(E1) 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 snr1(E1) and mutations in genes encoding other members of the Brm complex suggest that snr1(E1) mutant phenotypes result from reduced Brm complex function. Consistent with this view, SNR1(E1) 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 SNR1(E1) 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.
authors.affiliation: Department of Biology, Syracuse University, New York 13244-1270, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Marenda
authors.forename: Claudia B
authors.initials: CB
authors.lastname: Zraly
authors.forename: Yun
authors.initials: Y
authors.lastname: Feng
authors.forename: Susan
authors.initials: S
authors.lastname: Egan
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Dingwall
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D002843:Chromatin / Q000378:metabolism*; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D004625:Embryo, Nonmammalian; D005123:Eye / Q000254:growth & development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D007814:Larva; D008297:Male; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017933:Peripheral Nervous System / Q000254:growth & development / Q000378:metabolism; D021122:Protein Subunits; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014680:Veins / Q000254:growth & development; D014921:Wings, Animal / Q000098:blood supply / Q000254:growth & development
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D021122:Protein Subunits; C096659:Snr1 protein, Drosophila; D015534:Trans-Activators; D014157:Transcription Factors; C063460:Trl protein, Drosophila; C086469:brm protein, Drosophila