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Publication : Mammalian Heat Shock Response and Mechanisms Underlying Its Genome-wide Transcriptional Regulation.

First Author  Mahat DB Year  2016
Journal  Mol Cell Volume  62
Issue  1 Pages  63-78
PubMed ID  27052732 Mgi Jnum  J:253001
Mgi Id  MGI:6093980 Doi  10.1016/j.molcel.2016.02.025
Citation  Mahat DB, et al. (2016) Mammalian Heat Shock Response and Mechanisms Underlying Its Genome-wide Transcriptional Regulation. Mol Cell 62(1):63-78
abstractText  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.
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