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).