Genetic Screens for Enhancers of brahma Reveal Functional Interactions Between the BRM Chromatin-Remodeling Complex and the Delta-Notch Signal Transduction Pathway in Drosophila

摘要

The Drosophila trithorax group gene brahma ( brm ) encodes the ATPase subunit of a 2-MDa chromatin-remodeling complex. brm was identified in a screen for transcriptional activators of homeotic genes and subsequently shown to play a global role in transcription by RNA polymerase II. To gain insight into the targeting, function, and regulation of the BRM complex, we screened for mutations that genetically interact with a dominant-negative allele of brm ( brmK804R ). We first screened for dominant mutations that are lethal in combination with a brmK804R transgene under control of the brm promoter. In a distinct but related screen, we identified dominant mutations that modify eye defects resulting from expression of brmK804R in the eye-antennal imaginal disc. Mutations in three classes of genes were identified in our screens: genes encoding subunits of the BRM complex ( brm, moira , and osa ), other proteins directly involved in transcription ( zerknullt and RpII140 ), and signaling molecules ( Delta and vein ). Expression of brmK804R in the adult sense organ precursor lineage causes phenotypes similar to those resulting from impaired Delta-Notch signaling. Our results suggest that signaling pathways may regulate the transcription of target genes by regulating the activity of the BRM complex.