title: Hormone-response genes are direct in vivo regulatory targets of Brahma (SWI/SNF) complex function.
abstract: Metazoan SWI/SNF chromatin remodeling complexes exhibit ATP-dependent activation and repression of target genes. The Drosophila Brahma (SWI/SNF) complex subunits BRM and SNR1 are highly conserved with direct counterparts in yeast (SWI2/SNF2 and SNF5) and mammals (BRG1/hBRM and INI1/hSNF5). BRM encodes the catalytic ATPase required for chromatin remodeling and SNR1 is a regulatory subunit. Importantly, SNR1 mediates ATP-independent repression functions of the complex in cooperation with histone deacetylases and direct contacts with gene-specific repressors. SNR1 and INI1, as components of their respective SWI/SNF complexes, are important for developmental growth control and patterning, with direct function as a tumor suppressor. To identify direct regulatory targets of the Brm complex, we performed oligonucleotide-based transcriptome microarray analyses using RNA isolated from mutant fly strains harboring dominant-negative alleles of snr1 and brm. Steady-state RNA isolated from early pupae was examined, as this developmental stage critically requires Brm complex function. We found the hormone-responsive Ecdysone-induced genes (Eig) were strongly misregulated and that the Brm complex is directly associated with the promoter regions of these genes in vivo. Our results reveal that the Brm complex assists in coordinating hormone-dependent transcription regulation of the Eig genes.
authors.affiliation: Cardinal Bernardin Cancer Center, Oncology Institute and Department of Pathology, Loyola University of Chicago, Maywood, Illinois 60153, USA.
authors.forename: Claudia B
authors.initials: CB
authors.lastname: Zraly
authors.forename: Frank A
authors.initials: FA
authors.lastname: Middleton
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Dingwall
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics*; D004440:Ecdysone / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics*; D017344:Genes, Insect / Q000235:genetics; D007814:Larva / Q000378:metabolism; D009154:Mutation; D011679:Pupa / Q000378:metabolism; D034622:RNA Interference; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D029721:Drosophila Proteins; C096659:Snr1 protein, Drosophila; D015534:Trans-Activators; D014157:Transcription Factors; C086469:brm protein, Drosophila; D004440:Ecdysone