Issue 12, 2006

Genome-wide analysis of human HSF1 signaling reveals a transcriptional program linked to cellular adaptation and survival

Abstract

Although HSF1 plays an important role in the cellular response to proteotoxic stressors, little is known about the structure and function of the human HSF1 signaling network under both stressed and unstressed conditions. In this study, we used a combination of chromatin immunoprecipitation microarray analysis and time course gene expression microarray analysis with and without siRNA-mediated inhibition of HSF1 to comprehensively identify genes regulated directly and indirectly by HSF1. The correlation between promoter binding and gene expression was not significant for all genes bound by HSF1, suggesting that HSF1 binding per se is not sufficient for expression. However, the correlation with promoter binding was significant for genes identified as HSF1-regulated following siRNA knockdown. Among promoters bound by HSF1 following heat shock, a gene ontology analysis showed significant enrichment only in categories related to protein folding. In contrast, analysis of the extended HSF1 signaling network following siRNA knockdown showed enrichment in a variety of categories related to protein folding, anti-apoptosis, RNA splicing, ubiquitinylation and others, highlighting a complex transcriptional program regulated directly and indirectly by HSF1.

Graphical abstract: Genome-wide analysis of human HSF1 signaling reveals a transcriptional program linked to cellular adaptation and survival

Supplementary files

Article information

Article type
Paper
Submitted
02 May 2006
Accepted
07 Jun 2006
First published
23 Jun 2006

Mol. BioSyst., 2006,2, 627-639

Genome-wide analysis of human HSF1 signaling reveals a transcriptional program linked to cellular adaptation and survival

T. J. Page, D. Sikder, L. Yang, L. Pluta, R. D. Wolfinger, T. Kodadek and R. S. Thomas, Mol. BioSyst., 2006, 2, 627 DOI: 10.1039/B606129J

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