A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
HSFs drive transcription of distinct genes and enhancers during oxidative stress and heat shock
Tekijät: Himanen Samu V, Puustinen Mikael C, Da Silva Alejandro J, Vihervaara Anniina, Sistonen Lea
Kustantaja: OXFORD UNIV PRESS
Julkaisuvuosi: 2022
Journal: Nucleic Acids Research
Tietokannassa oleva lehden nimi: NUCLEIC ACIDS RESEARCH
Lehden akronyymi: NUCLEIC ACIDS RES
Vuosikerta: 50
Numero: 11
Aloitussivu: 6102
Lopetussivu: 6115
Sivujen määrä: 14
ISSN: 0305-1048
eISSN: 1362-4962
DOI: https://doi.org/10.1093/nar/gkac493
Verkko-osoite: https://academic.oup.com/nar/article/50/11/6102/6605316
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/175901777
Reprogramming of transcription is critical for the survival under cellular stress. Heat shock has provided an excellent model to investigate nascent transcription in stressed cells, but the molecular mechanisms orchestrating RNA synthesis during other types of stress are unknown. We utilized PRO-seq and ChIP-seq to study how Heat Shock Factors, HSF1 and HSF2, coordinate transcription at genes and enhancers upon oxidative stress and heat shock. We show that pause-release of RNA polymerase II (Pol II) is a universal mechanism regulating gene transcription in stressed cells, while enhancers are activated at the level of Pol II recruitment. Moreover, besides functioning as conventional promoter-binding transcription factors, HSF1 and HSF2 bind to stress-induced enhancers to trigger Pol II pause-release from poised gene promoters. Importantly, HSFs act at distinct genes and enhancers in a stress type-specific manner. HSF1 binds to many chaperone genes upon oxidative and heat stress but activates them only in heat-shocked cells. Under oxidative stress, HSF1 localizes to a unique set of promoters and enhancers to trans-activate oxidative stress-specific genes. Taken together, we show that HSFs function as multi-stress-responsive factors that activate distinct genes and enhancers when encountering changes in temperature and redox state.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
