Heat shock transcription factors (HSF, also designated HSTF) 1 and 2 are involved in this regulation. HSF1 and HSF2 are upregulated by estrogen, at both the mRNA and protein level. HSF1 is normally found as a monomer, whose transcriptional activity is repressed by constitutive phosphorylation. Upon activation, HSF1 forms trimers, gains DNA binding activity and is translocated to the nucleus. HSF2 activity is associated with differentiation and development, and, like HSF1, binds DNA as a trimer. HSF4 exists as two splice variants and is expressed in heart, brain and skeletal muscle as a homotrimer. HSF4a does not contain a DNA-binding domain and inhibits the formation of HSF1 nuclear bodies, thus repressing HSF1 mediated transcription. HSF4b does contain a DNA-binding domain and colocalizes with HSF1 nuclear bodies after heat shock.
