Transcription factors with helix-turn-helix (HTH) DNA-binding domains comprise 6 subclasses, characterized by the presence of a homeo domain, a paired box, a fork head / winged helix domain, heat shock factors (HSFs), tryptophan clusters, or a transcriptional enhancer factor (TEA) domain.Transcriptional activation of the heat shock response is orchestrated by heat shock factor 1 (HSF1), which rapidly translocates to hsp genes and induces their expression. Vertebrates have evolved a family of four HSF members, HSF1-4. HSF1 is constitutively expressed in most tissues and cell types and appears to be regulated primarily through posttranslational mechanisms. In addition to elevated temperatures or hyperthermia, HSF1 is activated by oxidative stress, heavy metals, and bacterial and viral infections, as well as by small-molecule modulators.