Activation of heat shock factor 2 during hemin-induced differentiation of human erythroleukemia cells

Mol Cell Biol. 1992 Sep;12(9):4104-11. doi: 10.1128/mcb.12.9.4104.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cell Differentiation / genetics*
  • DNA / metabolism
  • Gene Expression Regulation*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Hemin / physiology*
  • Hot Temperature
  • Humans
  • Kinetics
  • Leukemia, Erythroblastic, Acute
  • Molecular Sequence Data
  • Protein Binding
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • Heat-Shock Proteins
  • Transcription Factors
  • HSF2 protein, human
  • Hemin
  • DNA