title: Heat shock factor 1 promotes TERRA transcription and telomere protection upon heat stress.
abstract: In response to metabolic or environmental stress, cells activate powerful defense mechanisms to prevent the formation and accumulation of toxic protein aggregates. The main orchestrator of this cellular response is HSF1 (heat shock factor 1), a transcription factor involved in the up-regulation of protein-coding genes with protective roles. It has become very clear that HSF1 has a broader function than initially expected. Indeed, our previous work demonstrated that, upon stress, HSF1 activates the transcription of a non-coding RNA, named Satellite III, at pericentromeric heterochromatin. Here, we observe that the function of HSF1 extends to telomeres and identify subtelomeric DNA as a new genomic target of HSF1. We show that the binding of HSF1 to subtelomeric regions plays an essential role in the upregulation of non-coding TElomeric Repeat containing RNA (TERRA) transcription upon heat shock. Importantly, our data show that telomere integrity is impacted by heat shock and that telomeric DNA damages are markedly enhanced in HSF1 deficient cells. Altogether, our findings reveal a new direct and essential function of HSF1 in the transcriptional activation of TERRA and in telomere protection upon stress.
authors.affiliation: University Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, 38042 Grenoble Cedex 9, France.
authors.forename: Sivan
authors.initials: S
authors.lastname: Koskas
authors.affiliation: De Duve Institute and Catholic University of Louvain, GEPI, 1200 Brussels, Belgium.
authors.forename: Anabelle
authors.initials: A
authors.lastname: Decottignies
authors.affiliation: University Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, 38042 Grenoble Cedex 9, France.
authors.forename: Solenne
authors.initials: S
authors.lastname: Dufour
authors.affiliation: University Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, 38042 Grenoble Cedex 9, France.
authors.forename: Mylène
authors.initials: M
authors.lastname: Pezet
authors.affiliation: University Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, 38042 Grenoble Cedex 9, France.
authors.forename: André
authors.initials: A
authors.lastname: Verdel
authors.affiliation: University Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, 38042 Grenoble Cedex 9, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Vourc'h
authors.affiliation: University Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institute for Advanced Biosciences, 38042 Grenoble Cedex 9, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Faure
mesh_terms: D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors / Q000502:physiology*; D018869:Heat-Shock Response; D006801:Humans; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D059505:Telomere Homeostasis; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D062085:RNA, Long Noncoding