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http://hdl.handle.net/2445/171766
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DC Field | Value | Language |
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dc.contributor.author | Simonet, Nicolás G. | - |
dc.contributor.author | Thackray, Joshua K. | - |
dc.contributor.author | Vazquez, Berta N. | - |
dc.contributor.author | Ianni, Alessandro | - |
dc.contributor.author | Espinosa Alcantud, Maria | - |
dc.contributor.author | Morales Sanfrutos, Julia | - |
dc.contributor.author | Hurtado-Bagès, Sarah, 1990- | - |
dc.contributor.author | Sabidó Aguadé, Eduard | - |
dc.contributor.author | Buschbeck, Marcus | - |
dc.contributor.author | Tischfield, Jay | - |
dc.contributor.author | Torre Gómez, Carolina de la | - |
dc.contributor.author | Esteller, Manel | - |
dc.contributor.author | Braun, Thomas | - |
dc.contributor.author | Olivella, Mireia | - |
dc.contributor.author | Serrano, Lourdes | - |
dc.contributor.author | Vaquero, Alejandro | - |
dc.date.accessioned | 2020-11-05T12:23:48Z | - |
dc.date.available | 2020-11-05T12:23:48Z | - |
dc.date.issued | 2020-07-24 | - |
dc.identifier.issn | 2375-2548 | - |
dc.identifier.uri | http://hdl.handle.net/2445/171766 | - |
dc.description.abstract | Sirtuins are key players in the response to oxidative, metabolic and genotoxic stress, and are involved in genome stability, metabolic homeostasis and aging. Originally described as NAD+ -dependent deacetylases, some sirtuins are also characterized by a poorly understood mono-ADP-ribosyltransferase (mADPRT) activity. Here we report that the deacetylase SirT7 is a dual sirtuin as it also features auto-mADPRT activity. Molecular and structural evidence suggests that this novel activity occurs at a second previously undefined active site that is physically separated in another domain. Specific abrogation of this activity alters SirT7 chromatin distribution, suggesting a role for this modification in SirT7 chromatin binding specificity. We uncover an epigenetic pathway by which ADPribosyl-SirT7 is recognized by the ADP-ribose reader macroH2A1.1, a histone variant involved in chromatin organization, metabolism and differentiation. Glucose starvation (GS) boosts this interaction and promotes SirT7 relocalization to intergenic regions in a macroH2A1-dependent manner. Both SirT7 activities are in turn required to promote GS-dependent enrichment of macroH2A1 in a subset of nearby genes, which results in their specific up- or downregulation. Consistently, the expression changes of these genes associated to calorie restriction (CR) or aging are abrogated in SirT7-/- mice, reinforcing the link between Sirtuins, CR and aging. Our work provides a novel perspective about sirtuin duality and suggests a key role for SirT7/macroH2A1.1 axis in mammalian glucose homeostasis, calorie restriction signaling and aging. | - |
dc.format.extent | 16 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Association for the Advancement of Science | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1126/sciadv.aaz2590 | - |
dc.relation.ispartof | Science Advances, 2020, vol. 6, p. eaaz2590 | - |
dc.relation.uri | https://doi.org/10.1126/sciadv.aaz2590 | - |
dc.rights | cc-by-nc (c) Simonet et al., 2020 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/es | - |
dc.source | Articles publicats en revistes (Ciències Fisiològiques) | - |
dc.subject.classification | Estrès (Fisiologia) | - |
dc.subject.classification | Trastorns del metabolisme | - |
dc.subject.classification | Homeòstasi | - |
dc.subject.other | Stress (Physiology) | - |
dc.subject.other | Disorders of metabolism | - |
dc.subject.other | Homeostasis | - |
dc.title | SirT7 auto-ADP-ribosylation regulates glucose starvation response through macroH2A1 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 702428 | - |
dc.date.updated | 2020-11-05T12:23:48Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 32832656 | - |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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702428.pdf | 1.55 MB | Adobe PDF | View/Open |
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