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

Camille Dion, Stéphane Roche, Camille Laberthonnière, Natacha Broucqsault, Virginie Mariot, Shifeng Xue, Alexandra D. Gurzau, Agnieszka Nowak, Christopher T. Gordon, Marie Cécile Gaillard, Claire El-Yazidi, Morgane Thomas, Andrée Schlupp-Robaglia, Chantal Missirian, Valérie Malan, Liham Ratbi, Abdelaziz Sefiani, Bernd Wollnik, Bernard Binetruy, Emmanuelle Salort CampanaShahram Attarian, Rafaelle Bernard, Karine Nguyen, Jeanne Amiel, Julie Dumonceaux, James M. Murphy, Jérome Déjardin, Marnie E. Blewitt, Bruno Reversade, Jérome D. Robin, Frédérique Magdinier

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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 tomutations in factors thatmodify 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 dynamicmethylation of the D4Z4macrosatellite 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 newperspectives for understanding repetitive DNA sequences regulation.
Original languageEnglish (US)
Pages (from-to)2822-2839
Number of pages18
JournalNucleic acids research
Issue number6
StatePublished - Apr 8 2019
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-02-15

ASJC Scopus subject areas

  • Genetics


Dive into the research topics of 'SMCHD1 is involved in de novo methylation of the DUX4-encoding D4Z4 macrosatellite'. Together they form a unique fingerprint.

Cite this