title: Mammalian Heat Shock Response and Mechanisms Underlying Its Genome-wide Transcriptional Regulation.
abstract: The heat shock response (HSR) is critical for survival of all organisms. However, its scope, extent, and the molecular mechanism of regulation are poorly understood. Here we show that the genome-wide transcriptional response to heat shock in mammals is rapid and dynamic and results in induction of several hundred and repression of several thousand genes. Heat shock factor 1 (HSF1), the "master regulator" of the HSR, controls only a fraction of heat shock-induced genes and does so by increasing RNA polymerase II release from promoter-proximal pause. Notably, HSF2 does not compensate for the lack of HSF1. However, serum response factor appears to transiently induce cytoskeletal genes independently of HSF1. The pervasive repression of transcription is predominantly HSF1-independent and is mediated through reduction of RNA polymerase II pause release. Overall, mammalian cells orchestrate rapid, dynamic, and extensive changes in transcription upon heat shock that are largely modulated at pause release, and HSF1 plays a limited and specialized role.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA.
authors.forename: Dig B
authors.initials: DB
authors.lastname: Mahat
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA.
authors.forename: H Hans
authors.initials: HH
authors.lastname: Salamanca
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA.
authors.forename: Fabiana M
authors.initials: FM
authors.lastname: Duarte
authors.affiliation: Baker Institute for Animal Health, Cornell University, Ithaca, New York 14850, USA.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Danko
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14850, USA. Electronic address: jtl10@cornell.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Lis
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics*; D018869:Heat-Shock Response; D008322:Mammals / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D026362:Serum Response Factor / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C490017:Hsf1 protein, mouse; C531390:Hsf2 protein, mouse; D026362:Serum Response Factor; D014157:Transcription Factors; D012319:RNA Polymerase II