SirT7 auto-ADP-ribosylation regulates glucose starvation response through mH2A1
Por:
Simonet, NG, Thackray, JK, Vazquez, BN, Ianni, A, Espinosa-Alcantud, M, Morales-Sanfrutos, J, Hurtado-Bages, S, Sabido, E, Buschbeck, M, Tischfield, J, De La Torre, C, Esteller, M, Braun, T, Olivella, M, Serrano, L and Vaquero, A
Publicada:
1 jul 2020
Ahead of Print:
24 jul 2020
Resumen:
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.
Filiaciones:
:
Josep Carreras Leukaemia Res Inst IJC, Chromatin Biol Lab, Ctra Can Ruti,Cami Escoles S-N, Barcelona 08916, Spain
Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Chromatin Biol Lab, Av Gran Via Hosp 199-203, Barcelona 08908, Catalonia, Spain
Thackray, JK:
Rutgers State Univ, Dept Genet, 145 Bevier Rd, Piscataway, NJ 08854 USA
Rutgers State Univ, Human Genet Inst New Jersey, 145 Bevier Rd, Piscataway, NJ 08854 USA
:
Josep Carreras Leukaemia Res Inst IJC, Chromatin Biol Lab, Ctra Can Ruti,Cami Escoles S-N, Barcelona 08916, Spain
Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Chromatin Biol Lab, Av Gran Via Hosp 199-203, Barcelona 08908, Catalonia, Spain
Rutgers State Univ, Dept Genet, 145 Bevier Rd, Piscataway, NJ 08854 USA
Rutgers State Univ, Human Genet Inst New Jersey, 145 Bevier Rd, Piscataway, NJ 08854 USA
Ianni, A:
Max Planck Inst Heart & Lung Res, Dept Cardiac Dev & Remodelling, Bad Nauheim, Germany
:
Josep Carreras Leukaemia Res Inst IJC, Chromatin Biol Lab, Ctra Can Ruti,Cami Escoles S-N, Barcelona 08916, Spain
Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Chromatin Biol Lab, Av Gran Via Hosp 199-203, Barcelona 08908, Catalonia, Spain
Morales-Sanfrutos, J:
Barcelona Inst Sci & Technol BIST, Ctr Regulacio Genom CRG, Prote Unit, Barcelona, Catalonia, Spain
Univ Pompeu Fabra, Barcelona, Spain
:
Josep Carreras Leukaemia Res Inst IJC, Canc & Leukemia Epigenet & Biol Program, Campus ICO GTP UAB, Barcelona 08916, Catalonia, Spain
Sabido, E:
Barcelona Inst Sci & Technol BIST, Ctr Regulacio Genom CRG, Prote Unit, Barcelona, Catalonia, Spain
Univ Pompeu Fabra, Barcelona, Spain
:
Josep Carreras Leukaemia Res Inst IJC, Canc & Leukemia Epigenet & Biol Program, Campus ICO GTP UAB, Barcelona 08916, Catalonia, Spain
Germans Trias & Pujol Res Inst PMPPC IGTP, Program Predict & Personalized Med Canc, Barcelona 08916, Catalonia, Spain
Tischfield, J:
Rutgers State Univ, Dept Genet, 145 Bevier Rd, Piscataway, NJ 08854 USA
Rutgers State Univ, Human Genet Inst New Jersey, 145 Bevier Rd, Piscataway, NJ 08854 USA
De La Torre, C:
Josep Carreras Leukaemia Res Inst IJC, Prote Unit, Ctra Can Ruti,Cami Escoles S-N, Barcelona 08916, Catalonia, Spain
Bellvitge Biomed Res Inst IDIBELL, Prote Unit, Av Gran Via Hosp 199-203, Barcelona 08908, Catalonia, Spain
:
Josep Carreras Leukaemia Res Inst IJC, Canc Epigenet Grp, Barcelona, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid 28029, Spain
Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Catalonia, Spain
Univ Barcelona UB, Sch Med & Hlth Sci, Physiol Sci Dept, Barcelona, Catalonia, Spain
Braun, T:
Max Planck Inst Heart & Lung Res, Dept Cardiac Dev & Remodelling, Bad Nauheim, Germany
Olivella, M:
ESCI UPF, Sch Int Studies, Bioinformat Area, Barcelona, Catalonia, Spain
Univ Vic Univ Cent Catalunya UVIC UCC, UST, Bioinformat & Med Stat Grp, Barcelona, Catalonia, Spain
Serrano, L:
Rutgers State Univ, Dept Genet, 145 Bevier Rd, Piscataway, NJ 08854 USA
Rutgers State Univ, Human Genet Inst New Jersey, 145 Bevier Rd, Piscataway, NJ 08854 USA
CUNY, BMCC, Dept Sci, 199 Chambers St N699P, New York, NY 10007 USA
:
Josep Carreras Leukaemia Res Inst IJC, Chromatin Biol Lab, Ctra Can Ruti,Cami Escoles S-N, Barcelona 08916, Spain
Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Chromatin Biol Lab, Av Gran Via Hosp 199-203, Barcelona 08908, Catalonia, Spain
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