A1 Refereed original research article in a scientific journal
HSFs drive transcription of distinct genes and enhancers during oxidative stress and heat shock
Authors: Himanen Samu V, Puustinen Mikael C, Da Silva Alejandro J, Vihervaara Anniina, Sistonen Lea
Publisher: OXFORD UNIV PRESS
Publication year: 2022
Journal: Nucleic Acids Research
Journal name in source: NUCLEIC ACIDS RESEARCH
Journal acronym: NUCLEIC ACIDS RES
Volume: 50
Issue: 11
First page : 6102
Last page: 6115
Number of pages: 14
ISSN: 0305-1048
eISSN: 1362-4962
DOI: https://doi.org/10.1093/nar/gkac493
Web address : https://academic.oup.com/nar/article/50/11/6102/6605316
Self-archived copy’s web address: 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.
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