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

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Vihervaara A, Sergelius C, Vasara J, Blom MAH, Elsing AN, Roos-Mattjus P, Sistonen L
Förläggare: NATL ACAD SCIENCES
Publiceringsår: 2013
Tidskrift: Proceedings of the National Academy of Sciences
Tidskriftsakronym: P NATL ACAD SCI USA
Volym: 110
Nummer: 36
Artikelns första sida, sidnummer: E3388
Artikelns sista sida, sidnummer: E3397
Antal sidor: 10
ISSN: 0027-8424
eISSN: 1091-6490


Abstrakt

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.


Nyckelord

ChIP-seq, ENCODE, human genome, proteostasis

Senast uppdaterad 2019-12-12 vid 04:05