All organisms respond to elevated temperatures and a variety of environmental stresses by rapid synthesis of heat shock RNAs and proteins. The regulation of heat shock gene transcription is mediated by the transcriptional activator, heat shock factor (HSF), which binds to heat shock response elements (HSEs). These HSEs are found as three repeats of a 5-nucleotide {nGAAn} module, arranged in alternating orientation and present upstream of all heat shock genes. The HSEs are highly conserved among species yet HSF purified from yeast, Drosophila and human have different molecular weights and the proteins do not show significant immunological cross reaction. Two HSFs have been identified in human cells, HSF 1 and HSF 2, which bind to the same HSEs and have 38 % sequence identity. These factors are activated by distinct stimuli, HSF 1 is responsive to classical stress signals such as heat, heavy metals and oxidative reagents, whereas HSF 2 is activated during hemin-mediated differentiation of human erythroleukemia cells. HSF 1 exists constitutively in the cytoplasm and the nucleus of unstressed cells as a monomer which lacks DNA binding activity. Through an unknown signal generated during stress, HSF 1 becomes activated to a nuclear localized, trimeric state which binds to DNA. The phosphorylation of HSF 1 is necessary for maximal transcription of heat shock genes.Synonyms: HSF-1, HSTF1, Heat shock transcription factor 1