title: Epigenetic regulation of myogenic gene expression by heterochromatin protein 1 alpha.
abstract: Heterochromatin protein 1 (HP1) is an essential heterochromatin-associated protein typically involved in the epigenetic regulation of gene silencing. However, recent reports have demonstrated that HP1 can also activate gene expression in certain contexts including differentiation. To explore the role of each of the three mammalian HP1 family members (α, β and γ) in skeletal muscle, their expression was individually disrupted in differentiating skeletal myocytes. Among the three isoforms of HP1, HP1α was specifically required for myogenic gene expression in myoblasts only. Knockdown of HP1α led to a defect in transcription of skeletal muscle-specific genes including Lbx1, MyoD and myogenin. HP1α binds to the genomic region of myogenic genes and depletion of HP1α results in a paradoxical increase in histone H3 lysine 9 trimethylation (H3K9me3) at these sites. JHDM3A, a H3K9 demethylase also binds to myogenic gene's genomic regions in myoblasts in a HP1α-dependent manner. JHDM3A interacts with HP1α and knockdown of JHDM3A in myoblasts recapitulates the decreased myogenic gene transcription seen with HP1α depletion. These results propose a novel mechanism for HP1α-dependent gene activation by interacting with the demethylase JHDM3A and that HP1α is required for maintenance of myogenic gene expression in myoblasts.
authors.affiliation: Department of Medicine, Center for Cardiovascular Biology, Institute for Stem Cell Research, University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Patima
authors.initials: P
authors.lastname: Sdek
authors.forename: Kyohei
authors.initials: K
authors.lastname: Oyama
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Angelis
authors.forename: Shing S
authors.initials: SS
authors.lastname: Chan
authors.forename: Katja
authors.initials: K
authors.lastname: Schenke-Layland
authors.forename: W Robb
authors.initials: WR
authors.lastname: MacLellan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D015870:Gene Expression; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D023061:Gene Order; D056466:Histone Demethylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008745:Methylation; D051379:Mice; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism; D024510:Muscle Development / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D034622:RNA Interference
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D000090266:Chromobox Protein Homolog 5; D056466:Histone Demethylases