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| Status |
Public on Mar 01, 2016 |
| Title |
Mammalian Heat Shock Response And Mechanisms Underlying Its Genome-wide Transcriptional Regulation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Heat shock response (HSR) is critical for survival of organisms undergoing proteotoxic stress. Heat shock factor 1 (HSF1) is widely believed to be the master regulator of this response. Here, we examined the kinetics of the transcriptional response and HSF1 binding changes genome-wide after heat shock (HS) with high sensitivity and high spatial and temporal resolution using PRO-seq and ChIP-seq assays respectively in wild type and in hsf1-deletion mouse embryonic fibroblasts. The transcriptional response is rapid, dynamic, and extensive with activation of several hundred genes and repression of several thousands of genes. Although HSF1 is critically required for classical inducible Heat Shock Protein (HSP) genes, it is not required for the majority of gene activation. HSF1 acts mechanistically to promote RNA polymerase II (Pol II) release from the promoter-proximal pause, while recruitment and initiation of Pol II are predominantly HSF1-independent. Surprisingly, a major class of cytoskeleton genes is immediately (within 2.5 minutes) and transiently activated in an HSF1-independent manner. A second wave of regulation is characterized by robust activation or repression of new sets of genes. The broad repression of thousands of genes, a quarter of which are repressed immediately upon HS and the rest are repressed in the second wave of regulation, is mediated at the level of decreasing Pol II pause release and not at prior steps of Pol II recruitment or initiation. Notably, heat shock does not induce transcription of some previously defined HSP genes, and HSF2 – a homolog of HSF1 – does not compensate for the lack of HSF1. Together, these findings indicate that mammalian cells cope with stress by rapidly inducing pervasive and dramatic changes in transcription that are largely modulated at the step of pause release, and only a fraction of this regulation is HSF1-dependent.
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| Overall design |
Examination of transcriptional regulation before and after heat shock in WT, HSF1-/-, and HSF1&2-/- MEFs
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| Contributor(s) |
Mahat DB, Salamanca HH, Duarte F, Danko CG, Lis JT |
| Citation(s) |
27052732 |
| Submission date |
Aug 04, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Dig Bijay Mahat |
| E-mail(s) |
dbm222@cornell.edu
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| Organization name |
Cornell University
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| Department |
Molecular Biology & Genetics
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| Lab |
John Lis
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| Street address |
526 campus Rd
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| City |
Ithaca |
| State/province |
NY |
| ZIP/Postal code |
14853 |
| Country |
USA |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (33)
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| Relations |
| BioProject |
PRJNA291866 |
| SRA |
SRP062019 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE71708_RAW.tar |
1.6 Gb |
(http)(custom) |
TAR (of BIGWIG, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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