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Transcriptional response to stress in the dynamic chromatin environment of cycling and mitotic cells.

Heat shock factors (HSFs) are the master regulators of transcription under protein-damaging conditions, acting in an environment where the overall transcription is silenced. We determined the genomewide transcriptional program that is rapidly provoked by HSF1 and HSF2 under acute stress in human cel... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America September 3, 2013, Vol.110(36), pp.E3388-E3397
Main Author: Vihervaara, Anniina
Other Authors: Sergelius, Christian , Vasara, Jenni , Blom, Malin A H , Elsing, Alexandra N , Roos-Mattjus, Pia , Sistonen, Lea
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1305275110
Link: http://search.proquest.com/docview/1430396470/?pq-origsite=primo
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title: Transcriptional response to stress in the dynamic chromatin environment of cycling and mitotic cells.
format: Article
creator:
  • Vihervaara, Anniina
  • Sergelius, Christian
  • Vasara, Jenni
  • Blom, Malin A H
  • Elsing, Alexandra N
  • Roos-Mattjus, Pia
  • Sistonen, Lea
subjects:
  • Binding Sites–Genetics
  • Blotting, Western–Genetics
  • Cell Cycle–Genetics
  • Chromatin–Metabolism
  • DNA-Binding Proteins–Genetics
  • Gene Expression Regulation–Metabolism
  • Heat Shock Transcription Factors–Genetics
  • Heat-Shock Proteins–Metabolism
  • Heat-Shock Response–Genetics
  • Humans–Genetics
  • K562 Cells–Genetics
  • Male–Genetics
  • Mitosis–Genetics
  • Molecular Chaperones–Genetics
  • Polyubiquitin–Metabolism
  • Promoter Regions, Genetic–Metabolism
  • Protein Binding–Metabolism
  • RNA Interference–Metabolism
  • Reverse Transcriptase Polymerase Chain Reaction–Metabolism
  • Transcription Factors–Metabolism
  • Transcription, Genetic–Metabolism
  • Transcriptional Activation–Metabolism
  • Chromatin
  • DNA-Binding Proteins
  • Hsf1 Protein, Human
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Transcription Factors
  • Polyubiquitin
  • Hsf2 Protein, Human
  • Chip-Seq
  • Encode
  • Human Genome
  • Proteostasis
ispartof: Proceedings of the National Academy of Sciences of the United States of America, September 3, 2013, Vol.110(36), pp.E3388-E3397
description: Heat shock factors (HSFs) are the master regulators of transcription under protein-damaging conditions, acting in an environment where the overall transcription is silenced. We determined the genomewide transcriptional program that is rapidly provoked by HSF1 and HSF2 under acute stress in human cells. Our results revealed the molecular mechanisms that maintain cellular homeostasis, including HSF1-driven induction of polyubiquitin genes, as well as HSF1- and HSF2-mediated expression patterns of cochaperones, transcriptional regulators, and signaling molecules. We characterized the genomewide transcriptional response to stress also in mitotic cells where the chromatin is tightly compacted. We found a radically limited binding and transactivating capacity of HSF1, leaving mitotic cells highly susceptible to proteotoxicity. In contrast, HSF2 occupied hundreds of loci in the mitotic cells and localized to the condensed chromatin also in meiosis. These results highlight the importance of the cell cycle phase in transcriptional responses and identify the specific mechanisms for HSF1 and HSF2 in transcriptional orchestration. Moreover, we propose that HSF2 is an epigenetic regulator directing transcription throughout cell cycle progression.
language: eng
source:
identifier: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1305275110
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleTranscriptional response to stress in the dynamic chromatin environment of cycling and mitotic cells.
creatorVihervaara, Anniina ; Sergelius, Christian ; Vasara, Jenni ; Blom, Malin A H ; Elsing, Alexandra N ; Roos-Mattjus, Pia ; Sistonen, Lea
contributorVihervaara, Anniina (correspondence author) ; Vihervaara, Anniina (record owner)
ispartofProceedings of the National Academy of Sciences of the United States of America, September 3, 2013, Vol.110(36), pp.E3388-E3397
identifierE-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1305275110
subjectBinding Sites–Genetics ; Blotting, Western–Genetics ; Cell Cycle–Genetics ; Chromatin–Metabolism ; DNA-Binding Proteins–Genetics ; Gene Expression Regulation–Metabolism ; Heat Shock Transcription Factors–Genetics ; Heat-Shock Proteins–Metabolism ; Heat-Shock Response–Genetics ; Humans–Genetics ; K562 Cells–Genetics ; Male–Genetics ; Mitosis–Genetics ; Molecular Chaperones–Genetics ; Polyubiquitin–Metabolism ; Promoter Regions, Genetic–Metabolism ; Protein Binding–Metabolism ; RNA Interference–Metabolism ; Reverse Transcriptase Polymerase Chain Reaction–Metabolism ; Transcription Factors–Metabolism ; Transcription, Genetic–Metabolism ; Transcriptional Activation–Metabolism ; Chromatin ; DNA-Binding Proteins ; Hsf1 Protein, Human ; Heat Shock Transcription Factors ; Heat-Shock Proteins ; Molecular Chaperones ; Transcription Factors ; Polyubiquitin ; Hsf2 Protein, Human ; Chip-Seq ; Encode ; Human Genome ; Proteostasis
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descriptionHeat shock factors (HSFs) are the master regulators of transcription under protein-damaging conditions, acting in an environment where the overall transcription is silenced. We determined the genomewide transcriptional program that is rapidly provoked by HSF1 and HSF2 under acute stress in human cells. Our results revealed the molecular mechanisms that maintain cellular homeostasis, including HSF1-driven induction of polyubiquitin genes, as well as HSF1- and HSF2-mediated expression patterns of cochaperones, transcriptional regulators, and signaling molecules. We characterized the genomewide transcriptional response to stress also in mitotic cells where the chromatin is tightly compacted. We found a radically limited binding and transactivating capacity of HSF1, leaving mitotic cells highly susceptible to proteotoxicity. In contrast, HSF2 occupied hundreds of loci in the mitotic cells and localized to the condensed chromatin also in meiosis. These results highlight the importance of the cell cycle phase in transcriptional responses and identify the specific mechanisms for HSF1 and HSF2 in transcriptional orchestration. Moreover, we propose that HSF2 is an epigenetic regulator directing transcription throughout cell cycle progression.
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titleTranscriptional response to stress in the dynamic chromatin environment of cycling and mitotic cells.
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titleTranscriptional response to stress in the dynamic chromatin environment of cycling and mitotic cells.
authorVihervaara, Anniina ; Sergelius, Christian ; Vasara, Jenni ; Blom, Malin A H ; Elsing, Alexandra N ; Roos-Mattjus, Pia ; Sistonen, Lea
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