Elevated expression of heat shock factor (HSF) 2A stimulates HSF1-induced transcription during stress.
Heat shock factor 2 (HSF2) belongs to a family of structurally related transcription factors, which share the property of binding to heat shock elements in the promoters of hsp molecular chaperone genes. However, unlike HSF1, which is essential for hsp gene transcription, the cellular functions of HSF2 are not well known. Here we show that human HSF2, although an ineffective activator of the hsp70 promoter in vitro and in vivo in the absence of stress, participates in the activation of the hsp70 promoter by heat shock. HSF2 was not, however, activated by heat shock in cells deficient in functional HSF1, suggesting a requirement for HSF1 in HSF2-mediated transcriptional enhancement. In addition, HSF2 regulation involves differential activity of two isoforms, HSF2A and HSF2B, which arise from alternative splicing of a common hsf2 gene. Under basal conditions, both HSF2 isoforms are ineffective in activating the hsp70 transcription. However, heat shock differentially activates HSF2A in vivo. This phenomenon appears to be physiologically significant, as human myeloprogenitor cells differentiating along the erythroid lineage express HSF2A de novo and undergo a large increase in capacity to activate the hsp70 promoter. Our experiments further show that HSF1 is physically associated with HSF2 in the cell and that such binding is enhanced by heat shock. Our data suggest a mechanism involving the formation of heterocomplexes between HSF1 and HSF2 with enhanced activity to activate the hsp70 promoter when compared with HSF1 or HSF2 homotrimers.
He
Haiying
H
Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Soncin
Fabrice
F
Grammatikakis
Nicholas
N
Li
Youlin
Y
Siganou
Aliki
A
Gong
Jianlin
J
Brown
Steven A
SA
Kingston
Robert E
RE
Calderwood
Stuart K
SK
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins; D014157:Transcription Factors; C070389:HSF2 protein, human