Size doesn't matter in the heat shock response

Heat shock factor 1 (Hsf1) is a transcription factor that is often described as the master regulator of the heat shock response in all eukaryotes. However, due to its essentiality in yeast, Hsf1’s contribution to the transcriptome under basal and heat shock conditions has never been directly determined. Using a chemical genetics approach that allowed rapid Hsf1 inactivation, my colleagues and I have recently shown that the bulk of the heat shock response is Hsf1 independent. Rather than inducing genes responsible for carrying out the various cellular processes required for adaptation to thermal stress, Hsf1 controls a dedicated set of chaperone protein genes devoted to restoring protein-folding homeostasis. The limited scope of the Hsf1 regulon belies its outsize importance in cellular fitness.