Activation of Heat Shock Factor 2 during Hemin-Induced Differentiation of Human Erythroleukemia Cells

Lea Sistonen, Kevin D. Sarge, Benette Phillips, Klara Abravaya, Richard I. Morimoto

Research output: Contribution to journalArticlepeer-review

246 Scopus citations


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 beat 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.

Original languageEnglish
Pages (from-to)4104-4111
Number of pages8
JournalMolecular and Cellular Biology
Issue number9
StatePublished - Sep 1992

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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