title: Differential recognition of heat shock elements by members of the heat shock transcription factor family.
abstract: Heat shock transcription factor (HSF), an evolutionarily conserved stress response regulator, forms trimers and binds to heat shock element (HSE), comprising at least three continuous inverted repeats of the sequence 5'-nGAAn-3'. The single HSF of yeast is also able to bind discontinuously arranged nGAAn units. We investigated interactions between three human HSFs and various HSE types in vitro, in yeast cells, and in HeLa cells. Human HSF1, a stress-activated regulator, preferentially bound to continuous HSEs rather than discontinuous HSEs, and heat shock of HeLa cells caused expression of reporter genes containing continuous HSEs. HSF2, whose function is implicated in neuronal specification and spermatogenesis, exhibited a slightly higher binding affinity to discontinuous HSEs than did HSF1. HSF4, a protein required for ocular lens development, efficiently recognized discontinuous HSEs in a trimerization-dependent manner. Among four human gamma-crystallin genes encoding structural proteins of the lens, heat-induced HSF1 preferred HSEs on the gammaA-crystallin and gammaB-crystallin promoters, whereas HSF4 preferred HSE on the gammaC-crystallin promoter. These results suggest that the HSE architecture is an important determinant of which HSF members regulate genes in diverse cellular processes.
authors.affiliation: Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Takemori
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sakurai
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics / Q000502:physiology; D006801:Humans; D010641:Phenotype; D011401:Promoter Regions, Genetic; D050436:Regulatory Elements, Transcriptional; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D038222:gamma-Crystallins / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; C102948:HSF4 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D014157:Transcription Factors; D038222:gamma-Crystallins; C070389:HSF2 protein, human