title: Myogenin is a positive regulator of MEGF10 expression in skeletal muscle.
abstract: MEGF10 is known to function as a myogenic regulator of satellite cells in skeletal muscle. Mutations in MEGF10 gene cause a congenital myopathy called early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD). Despite its biological importance in muscle physiology, transcriptional regulation of the MEGF10 gene is unknown. Here, we characterized the 5' flanking region of the human MEGF10 gene and showed that the role of myogenic basic helix-loop-helix factor (bHLH) myogenin in MEGF10 transcription in muscle cells. Myogenin was found to share a similar expression pattern with MEGF10 during muscle regeneration and to increase the promoter activity of the MEGF10 gene in C2C12 cells. Overexpression of myogenin led to upregulation of MEGF10 mRNA in C2C12 cells. Site-directed mutagenesis assays revealed that the conserved E-box element at the region -114/-108 serves as a myogenin-binding motif. Promoter enzyme immunoassays and chromatin immunoprecipitation analysis showed direct interaction between myogenin and the myogenin-binding motif in the MEGF10 promoter. Taken together, these results indicate that myogenin is a positive regulator in transcriptional regulation of MEGF10 in skeletal muscle.
authors.affiliation: Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju 780-714, Republic of Korea. Electronic address: psyoon@dongguk.ac.kr.
authors.forename: Seung-Yoon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Youngeun
authors.initials: Y
authors.lastname: Yun
authors.affiliation: Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju 780-714, Republic of Korea.
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea; Biomedical Research Institute, Korea Institute Science and Technology, Seoul 136-791, Republic of Korea. Electronic address: iskim14@kist.re.kr.
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002460:Cell Line; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D018008:Myogenin / Q000502:physiology*; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D008565:Membrane Proteins; D018008:Myogenin; C525222:Megf10 protein, mouse
keywords: MEGF10; Myogenin; Skeletal muscle; Transcriptional regulation