Impact of heat shock transcription factor 1 on global gene expression profiles in cells which induce either cytoprotective or pro-apoptotic response following hyperthermia

Małgorzata Kus-Liśkiewicz,Joanna Polańska,Agnieszka Toma,Wiesława Widłak,Magdalena Olbryt,Natalia Vydra,Joanna Korfanty

doi:10.1186/1471-2164-14-456

Abstract

BackgroundElevated 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.ResultsTo 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.ConclusionsObserved 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.

Highlights

Elevated temperatures induce activation of the heat shock transcription factor 1 (HSF1) which in somatic cells leads to heat shock proteins synthesis and cytoprotection
As spermatogenic cells we used a fraction of cells enriched with spermatocytes, which are the most sensitive to damage at elevated temperatures [13]
Conclusions in somatic and spermatogenic cells after activation HSF1 binds to many promoters in a similar way, its impact on genes’ expression is completely different

Summary

Introduction

Elevated temperatures induce activation of the heat shock transcription factor 1 (HSF1) which in somatic cells leads to heat shock proteins synthesis and cytoprotection. Somatic cells protect themselves from damage during cellular stress inducing so called heat shock response, which results in heat shock proteins (HSPs) synthesis. Heat shock factor 1 (HSF1) is the primary transcription factor responsible for the activation of Hsp genes following stress. In Saccharomyces or Drosophila the direct transcriptional targets of HSF represent nearly 3% of genes [6,7] These genes encode for proteins involved in diverse cellular processes such as RNA splicing, apoptosis, ubiquitinylation and protein degradation, detoxification, energy generation, carbohydrate metabolism, small molecule transport, cell signaling and maintenance of cell integrity [6,7,8]

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