Transcriptional control by human heat shock factor one

The heat stress-induced transcriptional activator, heat shock factor one (HSF1) is responsible for coordinating the rapid transcriptional response of many heat shock protein genes, including the well-studied hsp70 gene. Induction of this gene by HSF1 is highly regulated and therefore provides a good model system in which to study activated transcription. In order to better understand the mechanisms that control heat shock induction, we established a biochemical system in which to search for HSF1-interacting proteins. We show that hHSF1 associates with BRG1, the ATPase subunit of human SWI/SNF, at endogenous protein concentrations, We also demonstrate that the transcriptional activation domains are responsible for this association, especially phenylalanine residues which have been shown to be involved in the promotion of transcriptional elongation on chromosomal templates. These results suggest that HSF1 may associate with the SWI/SNF complex for the purpose of stimulating elongation.; The repressive effect of chromatin supplies another layer of regulation in eukaryotic transcription. Chromatin remodeling complexes such as SWI/SNF use the energy of ATP hydrolysis to remodel nucleosomal DNA and increase transcription of nucleosomal templates. Activator-dependent targeting of chromatin remodeling complexes has been proposed as a mechanism for dealing with the nucleosomal architecture at inducible promoters. We demonstrate that HSF1, as well as other activators, are able to recruit human SWI/SNF to a nucleosomal template in a purified system. Again, mutations in the HSF1 activation domains that impaired its ability to stimulate a paused polymerase on the hsp70 gene also disrupted its ability to target SWI/SNF. This implies that a mechanism involving the recruitment of remodeling complexes may be partly responsible for the ability of HSF1 to promote elongation.