TISSUE-DEPENDENT EXPRESSION OF HEAT-SHOCK FACTOR-2 ISOFORMS WITH DISTINCT TRANSCRIPTIONAL ACTIVITIES

Heat shock factor 2 (HSF2) functions as a transcriptional regulator of heat shock protein gene expression in mammalian cells undergoing proc esses of differentiation and development, Our previous studies demonst rated high regulated expression and unusual constitutive DNA-binding a ctivity of the HSF2 protein in mouse testes, suggesting that HSF2 func tions to regulate heat shock protein gene expression in spermatogenic cells, The purpose of this study was to test whether HSF2 regulation i n testes is associated with alterations in the HSF2 polypeptide expres sed in testes relative to other mouse tissues, Our results show that m ouse cells express not one but two distinct HSF2 proteins and that the levels of these HSF2 isoforms are regulated in a tissue-dependent man ner, The testes express predominantly the 71-kDa HSF2-alpha isoform, w hile the heart and brain express primarily the 69-kDa HSF2-beta isofor m, These isoforms are generated by alternative splicing of HSF2 pre-mR NA, which results in the inclusion of an 18-amino-acid coding sequence in the HSF2-alpha mRNA that is skipped in the HSF2-beta mRNA, HSF2 al ternative splicing is also developmentally regulated, as our results r eveal a switch in expression from the HSE2-beta mRNA isoform to the HS F2-alpha isoform during testis postnatal development, Transfection ana lysis shows that the HSF2-alpha protein, the predominant isoform expre ssed in testis cells, is a more potent transcriptional activator than the HSF2-beta isoform, These results reveal a new mechanism for the co ntrol of HSF2 function in mammalian cells, in which regulated alternat ive splicing is used to modulate HSF2 transcriptional activity in a ti ssue-dependent manner.