title: Heterochromatin compaction is regulated by Suv4-20h1 to maintains skeletal muscle stem cells quiescence.
abstract: In this report, Boonsanay and colleagues describe a novel mechanism of maintenance of skeletal muscle stem cells [also known as satellite cells (SCs)] quiescence via the di-methyltransferase Suv4-20h1, regulator of heterochromatin formation. Conditional ablation of Suv4-20h1 in SCs leads notably to the loss of the histone modification H4K20me2 on the distal regulatory element of Myod combined with a relocation of the Myod locus toward a central position in the nucleus. This switch in nuclear compartment is correlated with decreased facultative H3K27me3 associated heterochromatin, and an increase in spontaneously activated MYOD-expressing SCs in homeostatic muscles. Consequently, Suv4-20h1 knock-out SCs demonstrate compromised stem cell potential, as they fail to efficiently self-renew and replenish the SC pool upon muscle injury. Strikingly, restoring MYOD expression alone rescues the levels of facultative chromatin and reverses the loss-of-quiescence phenotype.
authors.affiliation: 1 Inserm, IMRB U955-E10, 94000, Créteil, France ; 2 Faculté de Médecine, Université Paris Est Créteil, 94000, Créteil, France ; 3 Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France ; 4 Etablissement Francais du Sang, 94017, Créteil, France ; 5 APHP, Hopital Henri Mondor, DHU Pepsy & Centre de Référence des Maladies Neuromusculaires GNMH, 94000, Créteil, France.
authors.forename: Léo
authors.initials: L
authors.lastname: Machado
authors.affiliation: 1 Inserm, IMRB U955-E10, 94000, Créteil, France ; 2 Faculté de Médecine, Université Paris Est Créteil, 94000, Créteil, France ; 3 Ecole Nationale Vétérinaire d'Alfort, 94700, Maisons-Alfort, France ; 4 Etablissement Francais du Sang, 94017, Créteil, France ; 5 APHP, Hopital Henri Mondor, DHU Pepsy & Centre de Référence des Maladies Neuromusculaires GNMH, 94000, Créteil, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Relaix
keywords: H3K27me3; MYOD; Suv4-20h1; muscle regeneration; muscle stem cells; quiescence