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

L Sistonen, K D Sarge, B Phillips, K Abravaya, R I Morimoto

Research output: Contribution to journalArticleScientificpeer-review

246 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4104-11
Number of pages8
JournalMolecular and Cellular Biology
Volume12
Issue number9
DOIs
Publication statusPublished - Sept 1992
MoE publication typeA1 Journal article-refereed

Keywords

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

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