ACTIVATION OF HEAT-SHOCK FACTOR-II DURING HEMIN-INDUCED DIFFERENTIATION OF HUMAN ERYTHROLEUKEMIA CELLS

Lea Sistonen, KD SARGE, B PHILLIPS, K ABRAVAYA, RI MORIMOTO

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    Sammanfattning

    Hemin induces nonterminal differentiation of human K562 erythroleukemia cells, which is accompanied by the expression of certain erythroid cell-specific genes, such as the embryonic and fetal globins, and elevated expression of the stress genes hsp70, hsp90, and grp78/BiP. Previous studies revealed that, as during heat shock, transcriptional induction of hsp70 in hemin-treated cells is mediated by activation of heat shock transcription factor (HSF), which binds to the heat shock element (HSE). We report here that hemin activates the DNA-binding activity of HSF2, whereas heat shock induces predominantly the DNA-binding activity of a distinct factor, HSF1. This constitutes the first example of HSF2 activation in vivo. Both hemin and heat shock treatments resulted in equivalent levels of HSF-HSE complexes as analyzed in vitro by gel mobility shift assay, yet transcription of the hsp70 gene was stimulated much less by hemin-induced HSF than by heat shock-induced HSF. Genomic footprinting experiments revealed that hemin-induced HSF and heat shock-induced HSF, HSF2, and HSF1, respectively, occupy the HSE of the human hsp70 promoter in a similar yet not identical manner. We speculate that the difference in occupancy and/or in the transcriptional abilities of HSF1 and HSF2 accounts for the observed differences in the stimulation of hsp70 gene transcription.
    OriginalspråkOdefinierat/okänt
    Sidor (från-till)4104–4111
    Antal sidor8
    TidskriftMolecular and Cellular Biology
    Volym12
    Utgåva9
    StatusPublicerad - 1992
    MoE-publikationstypA1 Tidskriftsartikel-refererad

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