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 language | English |
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Pages (from-to) | 4104-11 |
Number of pages | 8 |
Journal | Molecular and Cellular Biology |
Volume | 12 |
Issue number | 9 |
DOIs | |
Publication status | Published - Sept 1992 |
MoE publication type | A1 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