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.
Keywords: H3K27me3; MYOD; Suv4-20h1; muscle regeneration; muscle stem cells; quiescence.