SNF/SWI COMPLEX AND TRANSCRIPTIONAL ACTIVATION

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Transcriptional activation involves a complex interplay between gene- specific activators, the general transcription apparatus, and chromatin. In the yeast Saccharomyces cerevisiae, the SNF/SWI complex has an important role in this process and is required for transcriptional activation of diverse genes. The SNF/SWI complex facilitates activation by gene-specific regulatory proteins and has been implicated in remodeling chromatin to overcome chromatin-mediated repression. The complex comprises eleven proteins (including SWI1/ADR6, SNF2/SWI2, SWI3, SNF5, SNF6 and SNF11) and has been widely conserved in eukaryotes. Homologous proteins have been identified in Drosophila and mammals, and a similar complex has been purified from human. In the yeast system, genetic approaches can be applied to provide insight into physiologically important functions of the SVF/SWI complex. This proposal focuses on analysis of the interactions of the complex with other proteins in vivo. Three of the projects concern functional characterization of proteins identified in a previous two-hybrid screen for interaction with SNF2. First one of these interacting proteins, MSN1, is a candidate for an adaptor between gene specific transcriptional activators and the SNF/SWI complex. An intensive analysis of MSN1 will be carried out to test this model. Second, genes encoding the catalytic subunits of cAMP-dependent protein kinase were recovered in the two-hybrid screen, and the relationship of this kinase activity to the SNF/SWI complex will be assessed. Third, seven as yet unidentified interacting proteins will be characterized with the goal of obtaining new insights into SNF/SWI function. Finally, an analysis of the function and interactions of the SNF6 protein will be initiated. Genetics evidence suggests that SNF6 has a distinct role from other SNF/SWI components and perhaps interacts directly with basal transcription factors. The proposed work will further our understanding of the functional interactions that occur between the SNF/SWI complex, transcription factors, and chromatin components during transcriptional activation of promoters in their native chromosomal context.