title: Impact of heat shock transcription factor 1 on global gene expression profiles in cells which induce either cytoprotective or pro-apoptotic response following hyperthermia.
abstract: BACKGROUND
  Elevated temperatures induce activation of the heat shock transcription factor 1 (HSF1) which in somatic cells leads to heat shock proteins synthesis and cytoprotection. However, in the male germ cells (spermatocytes) caspase-3 dependent apoptosis is induced upon HSF1 activation and spermatogenic cells are actively eliminated.
  
  
  RESULTS
  To elucidate a mechanism of such diverse HSF1 activity we carried out genome-wide transcriptional analysis in control and heat-shocked cells, either spermatocytes or hepatocytes. Additionally, to identify direct molecular targets of active HSF1 we used chromatin immunoprecipitation assay (ChIP) combined with promoter microarrays (ChIP on chip). Genes that are differently regulated after HSF1 binding during hyperthermia in both types of cells have been identified. Despite HSF1 binding to promoter sequences in both types of cells, strong up-regulation of Hsps and other genes typically activated by the heat shock was observed only in hepatocytes. In spermatocytes HSF1 binding correlates with transcriptional repression on a large scale. HSF1-bound and negatively regulated genes encode mainly for proteins required for cell division, involved in RNA processing and piRNA biogenesis.
  
  
  CONCLUSIONS
  Observed suppression of the transcription could lead to genomic instability caused by meiotic recombination disturbances, which in turn might induce apoptosis of spermatogenic cells. We propose that HSF1-dependent induction of cell death is caused by the simultaneous repression of many genes required for spermatogenesis, which guarantees the elimination of cells damaged during heat shock. Such activity of HSF1 prevents transmission of damaged genetic material to the next generation.
authors.affiliation: Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kus-Liśkiewicz
authors.forename: Joanna
authors.initials: J
authors.lastname: Polańska
authors.forename: Joanna
authors.initials: J
authors.lastname: Korfanty
authors.forename: Magdalena
authors.initials: M
authors.lastname: Olbryt
authors.forename: Natalia
authors.initials: N
authors.lastname: Vydra
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Toma
authors.forename: Wiesława
authors.initials: W
authors.lastname: Widłak
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000235:genetics*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D013090:Spermatocytes / Q000166:cytology* / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D014157:Transcription Factors; D004247:DNA