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Originally published as Genetics Published Articles Ahead of Print on June 8, 2005.
Genetics, Vol. 170, 1761-1774, August 2005, Copyright © 2005
doi:10.1534/genetics.105.041327
Genetic Screens for Enhancers of brahma Reveal Functional Interactions Between the BRM Chromatin-Remodeling Complex and the Delta-Notch Signal Transduction Pathway in Drosophila
Jennifer A. Armstrong*,1,
Adam S. Sperling*,
Renate Deuring*,
Laurina Manning
,
Sarah L. Moseley*,
Ophelia Papoulas*,2,
Caroline I. Piatek
,
Chris Q. Doe and
John W. Tamkun*,3
* Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California 95064
Institute of Neuroscience, Institute of Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, Oregon 97403-1254
Joint Science Department, Keck Science Center, The Claremont Colleges, Claremont, California, 91711
3 Corresponding author: Department of Molecular, Cell and Developmental Biology, University of California, 350 Sinsheimer Labs, Santa Cruz, CA 95064.
E-mail: tamkun{at}biology.ucsc.edu
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.
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