Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jul 8:14:456.
doi: 10.1186/1471-2164-14-456.

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  1 , Joanna Polańska, Joanna Korfanty, Magdalena Olbryt, Natalia Vydra, Agnieszka Toma, Wiesława Widłak
Affiliations

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 et al. BMC Genomics. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
General scheme of the study.
Figure 2
Figure 2
Monitoring of the heat shock response in isolated spermatocytes, testes and liver. Transcripts of selected Hsp genes up to 24 h after hyperthermia were detected by RT-PCR. Loading control reactions were performed with primers specific to 18S rRNA transcript; N, PCR negative control without template.
Figure 3
Figure 3
Kinetics of HSF1 activation. ChIP analysis of HSF1 binding to promoters of selected genes in hepatocytes and spermatocytes subjected to heat shock in different conditions (from 5 to 40 minutes, and temperatures 38°C or 43°C; hepatocytes were heat shocked only at 43°C). N, PCR-negative control without template.
Figure 4
Figure 4
Graphical representation of HSF1 binding to the promoters of Hsph1, Dnaja1 and Mov10l1 genes following hyperthermia in hepatocytes and spermatocytes. Results of ChIP on chip analysis are shown. Each line represents the signal from one probeset and is shown with reference to the position on the chromosome (numbered according to NCBIv36 of the mouse genome).
Figure 5
Figure 5
Binding of HSF1 estimated in ChIP on chip analysis to promoters of selected genes. (A) Binding at physiological and (B) elevated temperatures. HSF1 binding is calculated as AB1-AB0 mean signal in arbitrary units. *FDR > 0.05.
Figure 6
Figure 6
Overlap of genes affected by hyperthermia in hepatocytes and spermatocytes. Numbers of genes showing binding of HSF1 (A), modulated expression (B), and both (C). For HSF1 binding values AB1-AB0 ≥ 15 and FDR < 0.05 were taken into consideration; in the case of changes in expression level – range of SLR presented in Table 1.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kampinga HH, Hageman J, Vos MJ, Kubota H, Tanguay RM, Bruford EA, Cheetham ME, Chen B, Hightower LE. Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones. 2009;14:105–111. doi: 10.1007/s12192-008-0068-7. - DOI - PMC - PubMed
    1. Christians ES, Zhou Q, Renard J, Benjamin IJ. Heat shock proteins in mammalian development. Semin Cell Dev Biol. 2003;14:283–290. doi: 10.1016/j.semcdb.2003.09.021. - DOI - PubMed
    1. Rupik W, Jasik K, Bembenek J, Widłak W. The expression patterns of heat shock genes and proteins and their role during vertebrate’s development. Comp Biochem Physiol A Mol Integr Physiol. 2011;159:349–366. doi: 10.1016/j.cbpa.2011.04.002. - DOI - PubMed
    1. Lindquist S, Craig EA. The heat-shock proteins. Annu Rev Genet. 1988;22:631–677. doi: 10.1146/annurev.ge.22.120188.003215. - DOI - PubMed
    1. Voellmy R. On mechanisms that control heat shock transcription factor activity in metazoan cells. Cell Stress Chaperones. 2004;9:122–133. doi: 10.1379/CSC-14R.1. - DOI - PMC - PubMed

Publication types

Associated data