title: Regulation of Skeletal Muscle Stem Cell Quiescence by Suv4-20h1-Dependent Facultative Heterochromatin Formation.
abstract: Skeletal muscle stem cells (MuSCs) are required for regeneration of adult muscle following injury, a response that demands activation of mainly quiescent MuSCs. Despite the need for dynamic regulation of MuSC quiescence, relatively little is known about the determinants of this property. Here, we show that Suv4-20h1, an H4K20 dimethyltransferase, controls MuSC quiescence by promoting formation of facultative heterochromatin (fHC). Deletion of Suv4-20h1 reduces fHC and induces transcriptional activation and repositioning of the MyoD locus away from the heterochromatic nuclear periphery. These effects promote MuSC activation, resulting in stem cell depletion and impaired long-term muscle regeneration. Genetic reduction of MyoD expression rescues fHC formation and lost MuSC quiescence, restoring muscle regeneration capacity in Suv4-20h1 mutants. Together, these findings reveal that Suv4-20h1 actively regulates MuSC quiescence via fHC formation and control of the MyoD locus, thereby guarding and preserving the stem cell pool over a lifetime.
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Department of Cardiac Development and Remodeling, 61231 Bad Nauheim, Germany.
authors.forename: Verawan
authors.initials: V
authors.lastname: Boonsanay
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Department of Cardiac Development and Remodeling, 61231 Bad Nauheim, Germany.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Department of Cardiac Development and Remodeling, 61231 Bad Nauheim, Germany.
authors.forename: Angelina
authors.initials: A
authors.lastname: Georgieva
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Department of Cardiac Development and Remodeling, 61231 Bad Nauheim, Germany.
authors.forename: Sawa
authors.initials: S
authors.lastname: Kostin
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Department of Cardiac Development and Remodeling, 61231 Bad Nauheim, Germany.
authors.forename: Hui
authors.initials: H
authors.lastname: Qi
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Department of Cardiac Development and Remodeling, 61231 Bad Nauheim, Germany.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Department of Cardiac Development and Remodeling, 61231 Bad Nauheim, Germany. Electronic address: yonggang.zhou@mpi-bn.mpg.de.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Department of Cardiac Development and Remodeling, 61231 Bad Nauheim, Germany; Instituto de Investigacion en Biomedicina de Buenos Aires (IBioBA)-CONICET-Partner Institute of the Max Planck Society, C1425FQD Buenos Aires, Argentina. Electronic address: thomas.braun@mpi-bn.mpg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
mesh_terms: D000818:Animals; D002453:Cell Cycle; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006570:Heterochromatin / Q000378:metabolism* / Q000648:ultrastructure; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000166:cytology*; D009154:Mutation / Q000235:genetics; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology* / Q000648:ultrastructure
chemical_list: D006570:Heterochromatin; D017570:MyoD Protein; C570043:Suv4-20h protein, mouse; D011495:Histone-Lysine N-Methyltransferase
keywords: H3K27me3; MyoD; Suv4-20h1; long-term muscle regeneration; muscle stem cells; quiescence