Overexpression of HSF2-β inhibits hemin-induced heat shock gene expression and erythroid differentiation in K562 cells

Acquisition of heat shock factor 2 (HSF2) DNA binding activity is accompanied by induced transcription of heat shock genes in hemin-treated K562 cells undergoing erythroid differentiation. Previous studies revealed that HSF2 consists of two alternatively spliced isoforms, HSF2-α and HSF2- β, whose relative abundance is developmentally regulated and varies between different tissues. To investigate whether the molar ratio of HSF2-α and HSF2-β isoforms is crucial for the activation of HSF2 and whether the HSF2 isoforms play functionally distinct roles during the hemin-mediated erythroid differentiation, we generated cell clones expressing different levels of HSF2-α and HSF2-β. We show that in parental K562 cells, the HSF2-α isoform is predominantly expressed and HSF2 can be activated upon hemin treatment. In contrast, when HSF2-β is expressed at levels exceeding those of endogenous HSF2-α, the hemin-induced DNA binding activity and transcription of heat shock genes are repressed, whereas overexpression of HSF2-α results in an enhanced hemin response. Furthermore, the hemin-induced accumulation of globin, known as a marker of erythroid differentiation, is decreased in cells overexpressing HSF2-β. We suggest that HSF2-β acts as a negative regulator of HSF2 activity during hemin-mediated erythroid differentiation of K562 cells.