title: Incorporation of histone H3.1 suppresses the lineage potential of skeletal muscle.
abstract: Lineage potential is triggered by lineage-specific transcription factors in association with changes in the chromatin structure. Histone H3.3 variant is thought to play an important role in the regulation of lineage-specific genes. To elucidate the function of H3.3 in myogenic differentiation, we forced the expression of GFP-H3.1 to alter the balance between H3.1 and H3.3 in mouse C2C12 cells that could be differentiated into myotubes. GFP-H3.1 replaced H3.3 in the regulatory regions of skeletal muscle (SKM) genes and induced a decrease of H3K4 trimethylation (H3K4me3) and increase of H3K27 trimethylation (H3K27me3). Similar results were obtained by H3.3 knockdown. In contrast, MyoD-dependent H3.3 incorporation into SKM genes in fibroblasts induced an increase of H3K4me3 and H3K27me3. In mouse embryos, a bivalent modification of H3K4me3 and H3K27me3 was formed on H3.3-incorporated SKM genes before embryonic skeletal muscle differentiation. These results suggest that lineage potential is established through a selective incorporation of specific H3 variants that governs the balance of histone modifications.
authors.affiliation: Department of Advanced Medical Initiatives, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Harada
authors.affiliation: Department of Advanced Medical Initiatives, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Maehara
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan CREST, JST, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0021, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Laboratory for Cell Asymmetry, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
authors.forename: Daijiro
authors.initials: D
authors.lastname: Konno
authors.affiliation: Department Bioengineering, Graduate School of Engineering, Osaka City University, Osaka 558-8585, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Tachibana
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan CREST, JST, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0021, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Advanced Medical Initiatives, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan CREST, JST, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0021, Japan yohkawa@epigenetics.med.kyushu-u.ac.jp.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohkawa
mesh_terms: D000818:Animals; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology* / Q000378:metabolism; D011401:Promoter Regions, Genetic
chemical_list: D006657:Histones