2026-04-13T07:20:24Zhttps://recercat.cat/oai/requestoai:recercat.cat:2445/1717662025-12-05T09:34:26Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917
RECERCAT
author
Simonet, Nicolás G.
author
Thackray, Joshua K.
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Vazquez, Berta N.
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Ianni, Alessandro
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Espinosa Alcantud, Maria
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Morales Sanfrutos, Julia
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Hurtado-Bagès, Sarah, 1990-
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Sabidó Aguadé, Eduard
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Buschbeck, Marcus
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Tischfield, Jay
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Torre Gómez, Carolina de la
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Esteller, Manel
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Braun, Thomas
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Olivella, Mireia
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Serrano, Lourdes
author
Vaquero, Alejandro
2020-11-05T12:23:48Z2020-11-05T12:23:48Z2020-07-242020-11-05T12:23:48Z
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.
cc-by-nc (c) Simonet et al., 2020 http://creativecommons.org/licenses/by-nc/3.0/es info:eu-repo/semantics/openAccess
Estrès (Fisiologia)
Trastorns del metabolisme
Homeòstasi
Stress (Physiology)
Disorders of metabolism
Homeostasis
SirT7 auto-ADP-ribosylation regulates glucose starvation response through macroH2A1
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion