SirT7 auto-ADP-ribosylation regulates glucose starvation response through mH2A1
Simonet, Nicolas G.. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Thackray, J. K. (Department of Genetics. Human Genetics Institute of New Jersey. Rutgers University)
Vazquez Prat, Berta Nieves (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ianni, A. (Max Planck Institute for Heart and Lung Research. Department of Cardiac Development and Remodelling)
Espinosa-Alcantud, María Dolores (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Morales-Sanfrutos, J. (Universitat Pompeu Fabra)
Hurtado-Bagès, Sarah. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Sabidó, Eduard (Universitat Pompeu Fabra)
Buschbeck, Marcus (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Tischfield, J. (Department of Genetics. Human Genetics Institute of New Jersey. Rutgers University)
De La Torre Gómez, Gisela Carolina (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Esteller, M. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Braun, T. (Max Planck Institute for Heart and Lung Research. Department of Cardiac Development and Remodelling)
Olivella, Mireia (Universitat de Vic. Facultat de Ciències i Tecnologia)
Serrano, L. (Department of Science. BMCC. City University of New York (CUNY))
Vaquero, Alejandro (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	Sirtuins are key players of metabolic stress response. Originally described as deacetylases, some sirtuins also exhibit poorly understood mono-adenosine 5'-diphosphate (ADP)-ribosyltransferase (mADPRT) activity. We report that the deacetylase SirT7 is a dual sirtuin, as it also features auto-mADPRT activity. SirT7 mADPRT occurs at a previously undefined active site, and its abrogation alters SirT7 chromatin distribution. We identify an epigenetic pathway by which ADP-ribosyl-SirT7 is recognized by the ADP-ribose reader mH2A1. 1 under glucose starvation, inducing SirT7 relocalization to intergenic regions. SirT7 promotes mH2A1 enrichment in a subset of nearby genes, many of them involved in second messenger signaling, resulting in their specific up- or down-regulation. The expression profile of these genes under calorie restriction is consistently abrogated in SirT7-deficient mice, resulting in impaired activation of autophagy. Our work provides a novel perspective on sirtuin duality and suggests a role for SirT7/mH2A1. 1 axis in glucose homeostasis and aging.
Grants:	Ministerio de Economía y Competitividad SAF2011-25860 Ministerio de Economía y Competitividad SAF2014-55964-R Ministerio de Economía y Competitividad SAF2017-88975-R Ministerio de Economía y Competitividad SAF2016-77830-R Ministerio de Economía y Competitividad CTQ2016-80364-P Agència de Gestió d'Ajuts Universitaris i de Recerca 2014-SGR400 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR148 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR595 Instituto de Salud Carlos III PT17-0019
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	ADP-ribosylation ; Calorie restriction ; Expression profile ; Glucose homeostasis ; Intergenic regions ; Metabolic stress ; Second messenger ; Starvation response
Published in:	Science advances, Vol. 6 Núm. 30 (july 2020) , p. aaz2590, ISSN 2375-2548

DOI: 10.1126/sciadv.aaz2590
PMID: 32832656

17 p, 1.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles