Epigenomic signature of the progeroid Cockayne syndrome exposes distinct and common features with physiological ageing
| Autor: | Steve Horvath, Maria Giulia Bacalini, Claudio Franceschi, Paolo Garagnani, Claudia Chica, Miria Ricchetti, Clément Crochemore, Giovanna Lattanzi, Alain Sarasin |
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| Přispěvatelé: | Cellules Souches et Développement / Stem Cells and Development, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Sup'Biotech, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Karolinska Institutet [Stockholm], University hospital - Policlinico S.Orsola-Malpighi [Bologna, Italy], CNR Institute of Molecular Genetics 'Luigi Luca Cavalli-Sforza', Istituto Ortopedico Rizzoli [Bologna, Italy], University of California (UC), Institut Gustave Roussy (IGR), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Lobachevsky State University [Nizhni Novgorod], IRCCS Istituto delle Scienze Neurologiche di Bologna [Bologna, Italy], Ospedale Bellaria [Bologna, Italy], This work was supported by Agence Nationale de la Recherche (grant CS_AGE, aapg2019), DARRI (Institut Pasteur R&D, grant DISAGE, PasteurInnov2014), Programmes Transversales de Recherche, Institut Pasteur (grant PTR111-2017), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), University of California |
| Rok vydání: | 2021 |
| Předmět: |
Genetics
0303 health sciences Mutation DNA repair [SDV]Life Sciences [q-bio] dNaM Biology medicine.disease medicine.disease_cause Phenotype Cockayne syndrome 3. Good health 03 medical and health sciences 0302 clinical medicine DNA methylation medicine Epigenetics 030217 neurology & neurosurgery 030304 developmental biology Epigenomics |
| DOI: | 10.1101/2021.05.23.445308 |
| Popis: | Cockayne syndrome (CS) and UV-sensitivity syndrome (UVSS) are rare genetic disorders caused by mutation of the DNA repair and chromatin remodelling proteins CSA or CSB, but only CS patients display a progeroid and neurodegenerative phenotype. As epigenetic modifications constitute a well-established hallmark of ageing, we characterized genome-wide DNA methylation (DNAm) of fibroblasts from CS versus UVSS patients and healthy donors. The analysis of differentially methylated positions and regions revealed a CS-specific epigenetic signature, enriched in developmental transcription factors, transmembrane transporters, and cell adhesion factors. The CS-specific signature compared to DNAm changes in other progeroid diseases and regular ageing, identifyied commonalities and differences in epigenetic remodelling. CS shares DNAm changes with normal ageing more than other progeroid diseases do, and according to the methylation clock CS samples show up to 13-fold accelerated ageing. Thus, CS is characterized by a specific epigenomic signature that partially overlaps with and exacerbates DNAm changes occurring in physiological aging. Our results unveil new genes and pathways that are potentially relevant for the progeroid/degenerative CS phenotype. |
| Databáze: | OpenAIRE |
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