Differentiation lineage-specific expression of human heat shock transcription factor 2

Differentiation of multipotential hematopoietic cells into lineage-committe d precursors involves the selection and maintenance of appropriate programs of gene expression, regulated by specific transcription factors. Using hum an K562 erythroleukemia cells capable of differentiating along erythroid an d megakaryocytic lineages, we explore the differentiation-related role of h eat shock transcription factor 2 (HSF2), which belongs to a family of trans cription factors generally known to regulate heat shock gene expression. We demonstrate that enhanced HSF2 expression and the acquisition of HSF2 DNA binding activity are strictly specific for erythroid characteristics of K56 2 cells. Our results reveal a multistep regulatory process of HSF2 gene exp ression, In K562 cells undergoing hemin-mediated erythroid differentiation, the increase in HSF2 protein levels is preceded by transcriptional inducti on of the HSF2 gene, accompanied by increased HSF2 mRNA stability. In contr ast, during megakaryocytic differentiation induced by the phorbol ester TPA , expression of HSF2 is rapidly down-regulated, leading to a complete loss of the HSF2 protein. These results indicate that the determination of HSF2 expression occurs at the early stages of lineage commitment. Taken together , our data suggest that HSF2 could function as a lineage-restricted transcr iption factor during differentiation of K562 cells along either the erythro id or the megakaryocytic pathway.