SMCHD1 is involved in de novo methylation of the DUX4-encoding D4Z4 macrosatellite

Autor: Dion, Camille, Roche, Stéphane, Laberthonnière, Camille, Broucqsault, Natacha, Mariot, Virginie, Xue, Shifeng, Gurzau, Alexandra, Nowak, Agnieszka, Gordon, Christopher, Gaillard, Marie-Cécile, El-Yazidi, Claire, Thomas, Morgane, Robaglia-Schlupp, Andrée, Missirian, Chantal, Malan, Valérie, Ratbi, Liham, Sefiani, Abdelaziz, Wollnik, Bernd, Salort-Campana, Emmanuelle, Binétruy, Bernard, Attarian, Shahram, Bernard, Rafaelle, Nguyen, Karine, Amiel, Jeanne, Dumonceaux, Julie, Murphy, James, Déjardin, Jérôme, Blewitt, Marnie, Reversade, Bruno, Robin-Ducellier, Jérôme, Magdinier, Frédérique
Přispěvatelé: Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et génétique du diabète de type 1, génétique multifactorielle en endocrinologie pédiatrique (U986), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Hôpital de la Timone [CHU - APHM] (TIMONE), University Medical Center Göttingen (UMG), Centre de référence des maladies neuromusculaires et de la SLA, Département de génétique médicale [Hôpital de la Timone - APHM], Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), ANR-13-BSV1-0001,REPRAMIDE,Contrôle Central de la Reproduction chez la Femelle par les RFRPs, une nouvelle Famille de Peptides Hypothalamiques(2013), ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), Center for Reproductive Medicine, ACS - Diabetes & metabolism, ARD - Amsterdam Reproduction and Development, ACS - Heart failure & arrhythmias, Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University Medicine Goettingen, ANR-11-IDEX-0001-02/11-IDEX-0001,AMIDEX,AMIDEX(2011), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), AFM-Téléthon
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Cell biology
[SDV.BIO]Life Sciences [q-bio]/Biotechnology
Molecular biology
Chromosomal Proteins
Non-Histone
[SDV]Life Sciences [q-bio]
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Nose
Choanal Atresia
Epigenesis
Genetic
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Humans
Microphthalmos
ComputingMilieux_MISCELLANEOUS
Cells
Cultured
Homeodomain Proteins
Gene regulation
Chromatin and Epigenetics
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
DNA Methylation
Cellular Reprogramming
HCT116 Cells
Muscular Dystrophy
Facioscapulohumeral
Biological sciences
HEK293 Cells
Gene Expression Regulation
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Microsatellite Repeats
Zdroj: Nucleic Acids Research
Nucleic Acids Research, Oxford University Press, 2019, ⟨10.1093/nar/gkz005⟩
Nucleic acids research, 47(6), 2822-2839. Oxford University Press
iScience
iScience, 2022, 25 (2), pp.103757. ⟨10.1093/nar/gkz005⟩
ISSN: 0305-1048
1362-4962
2589-0042
Popis: The DNA methylation epigenetic signature is a key determinant during development. Rules governing its establishment and maintenance remain elusive especially at repetitive sequences, which account for the majority of methylated CGs. DNA methylation is altered in a number of diseases including those linked to mutations in factors that modify chromatin. Among them, SMCHD1 (Structural Maintenance of Chromosomes Hinge Domain Containing 1) has been of major interest following identification of germline mutations in Facio-Scapulo-Humeral Dystrophy (FSHD) and in an unrelated developmental disorder, Bosma Arhinia Microphthalmia Syndrome (BAMS). By investigating why germline SMCHD1 mutations lead to these two different diseases, we uncovered a role for this factor in de novo methylation at the pluripotent stage. SMCHD1 is required for the dynamic methylation of the D4Z4 macrosatellite upon reprogramming but seems dispensable for methylation maintenance. We find that FSHD and BAMS patient's cells carrying SMCHD1 mutations are both permissive for DUX4 expression, a transcription factor whose regulation has been proposed as the main trigger for FSHD. These findings open new questions as to what is the true aetiology for FSHD, the epigenetic events associated with the disease thus calling the current model into question and opening new perspectives for understanding repetitive DNA sequences regulation.
Databáze: OpenAIRE
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