GENETIC-ANALYSIS OF BRAHMA - THE DROSOPHILA HOMOLOG OF THE YEAST CHROMATIN REMODELING FACTOR SWI2 SNF2/

The Drosophila brahma (brm) gene encodes an activator of homeotic gene s related to the yeast chroma tin remodeling factor SWI2/SNF2. Here, w e report the phenotype of null and dominant-negative brm mutations. Us ing mosaic analysis, we found that the complete loss of brm function d ecreases cell viability and causes defects in the peripheral nervous s ystem of the adult. A dominant-negative brm mutation was generated by replacing a conserved lysine in the ATF-binding site of the BRM protei n with an arginine. This mutation eliminates brm function in vivo but does not affect assembly of the 2-MD BRM complex. Expression of the do minant-negative BRM protein caused peripheral nervous system defects, homeotic transformations, and decreased viability. Consistent with the se findings, the BRM protein is expressed at relatively high levels in nuclei throughout the developing organism. Site-directed mutagenesis was used to investigate the functions of conserved regions of the BRM protein. Domain II is essential for brm function and is required for t he assembly or stability of the BRM complex. In spite of its conservat ion in numerous eukaryotic regulatory proteins, the deletion of die br omodomain of the BRM protein has no discernible phenotype.