Kim S, Gross DS

The evolutionarily conserved Mediator complex is central to the regulation of gene transcription in eukaryotes, for it serves as a physical and functional interface between upstream regulators and the Pol II transcriptional machinery. Nonetheless, its role appears to be context dependent and the detailed mechanism by which it governs the ...

Read More

expression of most genes remains unknown. Here we investigate Mediator involvement in Heat Shock Protein (HSP) gene regulation in the yeast Saccharomyces cerevisiae. We find that in response to thermal upshift, subunits representative of each of the four Mediator modules - Head, Middle, Tail and Kinase - are rapidly, robustly and selectively recruited to the promoter regions of HSP genes. Their residence is transient, returning to near-background levels within 90 min. Heat Shock Factor 1 (Hsf1) plays a central role in recruiting Mediator as indicated by the fact that truncation of either its N- or C-terminal activation domain significantly reduces Mediator occupancy, while removal of both activation domains abolishes it. Likewise, ablation of either of two Mediator Tail subunits, Med15 or Med16, reduces Mediator recruitment to HSP promoters, while deletion of both abolishes it. Accompanying loss of Mediator, recruitment of RNA Pol II is substantially diminished. Interestingly, Mediator antagonizes Hsf1's constitutive occupancy of non-induced promoters yet facilitates enhanced Hsf1 association with activated ones. Collectively, our observations indicate that Hsf1, via its dual activation domains, recruits holo-Mediator to HSP promoters in response to acute heat stress through cooperative physical and/or functional interactions with the Tail module.

Date: Feb. 27, 2013

View in: Pubmed Google Scholar

151226