Stress-induced HSF1 trimerization results in the increased affinity of HSF1 for the heat shock elements (HSE) usually located within promoters of HSF1 target genes (Sarge KD et al. 1993; Wang Y and Morgan WD 1994; Herbomel G et al. 2013). HSEs are highly conserved and consist of contiguous inverted repeats of pentameric sequence nGAAn (i.e., nGAAnnTTCnnGAAn) (Abravaya K et al. 1991; Sarge KD et al. 1993; Cunniff NFA & Morgan WD 1993). The promoters of HSF target genes can contain more than one HSE, suggesting that the HSF1-HSE interaction may occur in cooperative manner when the binding of HSF trimer to HSE facilitates binding of the next HSF1 trimer (Wang Y and Morgan WD 1994).
Replication protein A (RPA), which is involved in DNA metabolism, was shown to support transcription factor access to nucleosomal DNA as a scaffold for HSF1 and a histone chaperone, FACT (Fujimoto M et al. 2012).
Mutagenesis analysis revealed that DNA binding domain of human HSF1 is required for HSF1 binding to HSE and for nuclear stress bodies (nSBs) formation (Westerheide SD et al. 2009; Herbomel G et al. 2013).
While HSF1 can bind to promoters of many genes targets with or without inducing their transcription, it is best known for stress-induced regulatory functions on certain chaperone genes, such as HSPA1A/HSP70, HSPC/HSP90, HSPB1/HSP27, and DNAJB1/HSP40 (Mosser DD et al. 1988; Trinklein ND et al. 2004a,b; Page TG et al. 2006). At the same time, however, the constitutive expression of hsp70, hsp60, BiP/GRP78, and hsp27 in cultured embryonic murine cells was unaffected by the disruption of the hsf1 gene (McMillan et al. 1998). This is additionally supported by findings that the production of HSP70 was not induced after transfection of HSF1 into human epidermoid A431 cells despite the fact that HSF1 was found to bind HSE on hsp70 gene. While HSP70 production was not altered in unstressed cells, the treatment with phorbol 12-myristate 13-acetate (PMA) increased the HSP70 level in A431 cells and reached even higher expression level in HSF1-transfected A431 cells (Ding XZ et al. 1997). Thus, HSF1 is required for stress-induced upregulation of hsp genes while may not be involved in their basal expression (as was shown in higher eukaryotes).