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http://hdl.handle.net/2445/171766
Title: | SirT7 auto-ADP-ribosylation regulates glucose starvation response through macroH2A1 |
Author: | Simonet, Nicolás G. Thackray, Joshua K. Vazquez, Berta N. Ianni, Alessandro Espinosa Alcantud, Maria Morales Sanfrutos, Julia Hurtado-Bagès, Sarah, 1990- Sabidó Aguadé, Eduard Buschbeck, Marcus Tischfield, Jay Torre Gómez, Carolina de la Esteller, Manel Braun, Thomas Olivella, Mireia Serrano, Lourdes Vaquero, Alejandro |
Keywords: | Estrès (Fisiologia) Trastorns del metabolisme Homeòstasi Stress (Physiology) Disorders of metabolism Homeostasis |
Issue Date: | 24-Jul-2020 |
Publisher: | American Association for the Advancement of Science |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1126/sciadv.aaz2590 |
It is part of: | Science Advances, 2020, vol. 6, p. eaaz2590 |
URI: | http://hdl.handle.net/2445/171766 |
Related resource: | https://doi.org/10.1126/sciadv.aaz2590 |
ISSN: | 2375-2548 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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