CBP-HSF2 structural and functional interplay in Rubinstein-Taybi neurodevelopmental disorder.

Autor: de Thonel A; Université de Paris, CNRS, Epigenetics and Cell Fate, F-75013, Paris, France. aurelie.dethonel@univ-paris-diderot.fr., Ahlskog JK; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, Finland.; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland., Daupin K; Université de Paris, CNRS, Epigenetics and Cell Fate, F-75013, Paris, France., Dubreuil V; Université de Paris, CNRS, Epigenetics and Cell Fate, F-75013, Paris, France., Berthelet J; Université de Paris, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France., Chaput C; Université de Paris, CNRS, Epigenetics and Cell Fate, F-75013, Paris, France.; Ksilink, Strasbourg, France., Pires G; Université de Paris, CNRS, Epigenetics and Cell Fate, F-75013, Paris, France., Leonetti C; Université de Paris, CNRS, Epigenetics and Cell Fate, F-75013, Paris, France., Abane R; Université de Paris, CNRS, Epigenetics and Cell Fate, F-75013, Paris, France., Barris LC; Laboratory of Molecular Regulation of Neurogenesis, GIGA-Stem Cells and GIGA-Neurosciences, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, CHU Sart Tilman, Liège, Belgium., Leray I; Université de Nantes, CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016, CNRS UMS 3556, F-44000, Nantes, France., Aalto AL; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, Finland.; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland., Naceri S; Université de Paris, CNRS, Epigenetics and Cell Fate, F-75013, Paris, France., Cordonnier M; INSERM, UMR1231, Laboratoire d'Excellence LipSTIC, Dijon, France.; University of Bourgogne Franche-Comté, Dijon, France.; Département d'Oncologie médicale, Centre Georges-François Leclerc, Dijon, France., Benasolo C; Université de Paris, CNRS, Epigenetics and Cell Fate, F-75013, Paris, France., Sanial M; CNRS, UMR 7592 Institut Jacques Monod, F-75205, Paris, France., Duchateau A; Université de Paris, CNRS, Epigenetics and Cell Fate, F-75013, Paris, France., Vihervaara A; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, Finland.; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.; KTH Royal Institute of Technology, Stockholm, Sweden., Puustinen MC; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, Finland.; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland., Miozzo F; Université de Paris, CNRS, Epigenetics and Cell Fate, F-75013, Paris, France.; Neuroscience Institute-CNR (IN-CNR), Milan, Italy., Fergelot P; Department of Medical Genetics, University Hospital of Bordeaux, Bordeaux, France and INSERM U1211, University of Bordeaux, Bordeaux, France., Lebigot É; Service de Biochimie-pharmaco-toxicologie, Hôpital Bicêtre, Hopitaux Universitaires Paris-Sud, 94270 Le Kremlin Bicêtre, Paris-Sud, France., Verloes A; Université de Paris, INSERM, NeuroDiderot, Robert-Debré Hospital, F-75019, Paris, France.; Genetics Department, AP-HP, Robert-Debré University Hospital, Paris, France., Gressens P; Université de Paris, INSERM, NeuroDiderot, Robert-Debré Hospital, F-75019, Paris, France., Lacombe D; Department of Medical Genetics, University Hospital of Bordeaux, Bordeaux, France and INSERM U1211, University of Bordeaux, Bordeaux, France., Gobbo J; INSERM, UMR1231, Laboratoire d'Excellence LipSTIC, Dijon, France.; University of Bourgogne Franche-Comté, Dijon, France.; Département d'Oncologie médicale, Centre Georges-François Leclerc, Dijon, France., Garrido C; INSERM, UMR1231, Laboratoire d'Excellence LipSTIC, Dijon, France.; University of Bourgogne Franche-Comté, Dijon, France.; Département d'Oncologie médicale, Centre Georges-François Leclerc, Dijon, France., Westerheide SD; Department of Cell Biology, Microbiology, and Molecular Biology, College of Arts and Sciences, University of South Florida, Tampa, FL, USA., David L; Université de Nantes, CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016, CNRS UMS 3556, F-44000, Nantes, France., Petitjean M; Université de Paris, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France., Taboureau O; Université de Paris, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France., Rodrigues-Lima F; Université de Paris, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France., Passemard S; Université de Paris, INSERM, NeuroDiderot, Robert-Debré Hospital, F-75019, Paris, France., Sabéran-Djoneidi D; Université de Paris, CNRS, Epigenetics and Cell Fate, F-75013, Paris, France., Nguyen L; Laboratory of Molecular Regulation of Neurogenesis, GIGA-Stem Cells and GIGA-Neurosciences, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, CHU Sart Tilman, Liège, Belgium., Lancaster M; MRC Laboratory of Molecular Biology, Cambridge Biomedical, Campus, Cambridge, UK., Sistonen L; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, Finland.; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland., Mezger V; Université de Paris, CNRS, Epigenetics and Cell Fate, F-75013, Paris, France. valerie.mezger@univ-paris-diderot.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Nov 16; Vol. 13 (1), pp. 7002. Date of Electronic Publication: 2022 Nov 16.
DOI: 10.1038/s41467-022-34476-2
Abstrakt: Patients carrying autosomal dominant mutations in the histone/lysine acetyl transferases CBP or EP300 develop a neurodevelopmental disorder: Rubinstein-Taybi syndrome (RSTS). The biological pathways underlying these neurodevelopmental defects remain elusive. Here, we unravel the contribution of a stress-responsive pathway to RSTS. We characterize the structural and functional interaction between CBP/EP300 and heat-shock factor 2 (HSF2), a tuner of brain cortical development and major player in prenatal stress responses in the neocortex: CBP/EP300 acetylates HSF2, leading to the stabilization of the HSF2 protein. Consequently, RSTS patient-derived primary cells show decreased levels of HSF2 and HSF2-dependent alteration in their repertoire of molecular chaperones and stress response. Moreover, we unravel a CBP/EP300-HSF2-N-cadherin cascade that is also active in neurodevelopmental contexts, and show that its deregulation disturbs neuroepithelial integrity in 2D and 3D organoid models of cerebral development, generated from RSTS patient-derived iPSC cells, providing a molecular reading key for this complex pathology.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz: