HSF2

Heat shock factor 2 (HSF2) is a transcription factor that belongs to the heat shock factor (HSF) family. In humans, the HSF2 gene encodes a protein that binds to heat shock elements (HSEs) in the promoters of heat shock protein genes and other targets, regulating transcription in response to cellular stress as well as developmental cues. HSF2 shares the conserved DNA-binding, oligomerization, and regulatory domains characteristic of HSFs and can form homotrimers or heterotrimers with other HSF family members under certain conditions.

Expression of HSF2 is widespread, with prominent levels in the brain and gonads, and it plays a role in development and differentiation. Unlike the canonical rapid activation of HSF1 during acute heat stress, HSF2 activity is often linked to developmental programs and cellular maturation, and it can modulate the cellular heat shock response by regulating a subset of chaperone genes and other stress-responsive targets.

HSF2 activity is regulated by post-translational modifications, subcellular localization, and interactions with molecular chaperones such as HSP70 and HSP90, as well as with other transcription factors. It can form trimers that bind DNA and, depending on context, may act as a transcriptional activator or modulator of gene expression. HSF2 can also participate in the formation of heteromeric complexes with other HSFs, influencing the output of the heat shock response.

Research on HSF2 has focused on development, neural differentiation, and fertility, with studies in animal models indicating roles in brain development and spermatogenesis. Ongoing research seeks to define the full spectrum of HSF2 target genes and its functions in health and disease.