USP7/Maged1-mediated H2A monoubiquitination in the paraventricular thalamus: an epigenetic mechanism involved in cocaine use disorder

Cheron, Julian; Beccari, Leonardo; Hagué, Perrine; Icick, Romain; Despontin, Chloé; Carusone, Teresa; Defrance, Matthieu; Bhogaraju, Sagar; Martín García, Elena, 1975-; Capellan, Roberto; Maldonado, Rafael, 1961-; Vorspan, Florence; Bonnefont, Jérôme; d'Exaerde, Alban de Kerchove

USP7/Maged1-mediated H2A monoubiquitination in the paraventricular thalamus: an epigenetic mechanism involved in cocaine use disorder

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dc.contributor.author Cheron, Julian
dc.contributor.author Beccari, Leonardo
dc.contributor.author Hagué, Perrine
dc.contributor.author Icick, Romain
dc.contributor.author Despontin, Chloé
dc.contributor.author Carusone, Teresa
dc.contributor.author Defrance, Matthieu
dc.contributor.author Bhogaraju, Sagar
dc.contributor.author Martín García, Elena, 1975-
dc.contributor.author Capellan, Roberto
dc.contributor.author Maldonado, Rafael, 1961-
dc.contributor.author Vorspan, Florence
dc.contributor.author Bonnefont, Jérôme
dc.contributor.author d'Exaerde, Alban de Kerchove
dc.date.accessioned 2024-02-06T07:24:49Z
dc.date.available 2024-02-06T07:24:49Z
dc.date.issued 2023
dc.description.abstract The risk of developing drug addiction is strongly influenced by the epigenetic landscape and chromatin remodeling. While histone modifications such as methylation and acetylation have been studied in the ventral tegmental area and nucleus accumbens (NAc), the role of H2A monoubiquitination remains unknown. Our investigations, initially focused on the scaffold protein melanoma-associated antigen D1 (Maged1), reveal that H2A monoubiquitination in the paraventricular thalamus (PVT) significantly contributes to cocaine-adaptive behaviors and transcriptional repression induced by cocaine. Chronic cocaine use increases H2A monoubiquitination, regulated by Maged1 and its partner USP7. Accordingly, Maged1 specific inactivation in thalamic Vglut2 neurons, or USP7 inhibition, blocks cocaine-evoked H2A monoubiquitination and cocaine locomotor sensitization. Additionally, genetic variations in MAGED1 and USP7 are linked to altered susceptibility to cocaine addiction and cocaine-associated symptoms in humans. These findings unveil an epigenetic modification in a non-canonical reward pathway of the brain and a potent marker of epigenetic risk factors for drug addiction in humans.
dc.description.sponsorship We thank the EMBL Proteomics Core Facility. JC is a research fellow of FRS-FNRS and Fonds Erasme. LB is a Ramon y Cajal fellow (CBMSO). AKE is a research director of the FRS-FNRS and a WELBIO investigator. Funding was provided by FRS-FNRS grants 23587797, 33659288, 33659296 (A.K.E.), WELBIO grant 30256053 (A.K.E.), Fondation Simone et Pierre Clerdent 2018 Prize (A.K.E.), Fondation ULB (A.K.E.), Fondation Cigrang (A.K.E.), Dotation Jeune Chercheur INSERM (L.B.), AFM stratégique 2 MyoNeurAlp (L.B.), Agence Nationale pour la Recherche grant ANR- 21-CE11-0013 (S.B.), EMBL Interdisciplinary Postdocs (EIPOD4) initiative co-funded by Marie Skłodowska-Curie (grant 847543) (T.C.), Mission Inter-Ministérielle de Lutte Contre la Drogue et la Toxicomanie grant ASE07082KSA (F.V.), Direction de la Recherche Clinique et du Développement de l’Assistance Publique − Hôpitaux de Paris grant OST07013 (F.V.), French Ministry of Health, Programme Hospitalier de Recherche Clinique National AOM10165 (F.V.).
dc.format.mimetype application/pdf
dc.identifier.citation Cheron J, Beccari L, Hagué P, Icick R, Despontin C, Carusone T, Defrance M, Bhogaraju S, Martin-Garcia E, Capellan R, Maldonado R, Vorspan F, Bonnefont J, de Kerchove d'Exaerde A. USP7/Maged1-mediated H2A monoubiquitination in the paraventricular thalamus: an epigenetic mechanism involved in cocaine use disorder. Nat Commun. 2023 Dec 20;14(1):8481. DOI: 10.1038/s41467-023-44120-2
dc.identifier.doi http://dx.doi.org/10.1038/s41467-023-44120-2
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/58961
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nat Commun. 2023 Dec 20;14(1):8481
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/847543
dc.rights © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Addiction
dc.subject.keyword Epigenetics in the nervous system
dc.title USP7/Maged1-mediated H2A monoubiquitination in the paraventricular thalamus: an epigenetic mechanism involved in cocaine use disorder
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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