Our group has continued studies of chromatin structure and the regulation of heat shock gene expression, with emphasis on the structure and function of the heat shock transcription factor (HSF) and on the remodeling of the heat shock gene promoter in chromatin. Protease mapping of the global physical structure of HSF and characterization of Drosophila carrying mutations in the HSF gene was completed. The genetic studies revealed a novel developmental function for HSF that appears to be unrelated to its characteristic activity as a stress-responsive transcriptional activator. Biophysical studies of HSF oligomerization were initiated in order to determine the equilibrium dissociation constants for the monomer-trimer transition, the first step of HSF activation by heat shock. Our group has also continued work on the ATP-dependent nucleosome remodeling factor (NURF) discovered in this laboratory. Two additional subunits of NURF (NURF-55 and NURF 38) have been characterized. NURF-55 was discovered to be related to RbAp48, a protein previously found to bind in vitro to retinoblastoma and currently found as a component of several protein complexes involved in histone metabolism. We are currently analyzing the role of NURF in facilitating transcriptional stimulation of chromatin templates in vitro and are investigating the structural determinants of nucleosomes that are essential for the activity of NURF in reconfiguring nucleosome structure.
