title: The virtual element in proximal promoter of porcine myostatin is regulated by myocyte enhancer factor 2C.
abstract: Myostatin (myostatin) is a member of the transforming growth factor-β superfamily. In this study, we investigated the transcriptional regulation of porcine myostatin expression in C2C12 cells. Sequence analysis of 2kb of the porcine myostatin gene upstream region revealed that it contains 16 E-box motifs. Using a serial deletion strategy, we identified a vital enhancer region between nucleotides -218 and -137 in promoter region of porcine myostatin. Gel-shift assay and deletion analysis result showed F1 site, from nucleotides -206 to -189, was the key element to produce the promoter/nucleus extract complex, which directly interact with transcriptional factor MEF2C. Overexpression of MEF2C increased myostatin promoter activity in dose dependent manner; and whereas introducing of small interfering RNA to MEF2C produced the opposite effect in both myoblasts and myotubes. When endogenous MEF2C was knocked down, the complex of protein/F1 was attenuated, and myostatin mRNA and protein level was also decreased. Thus, we propose that MEF2C could modulate and restrain myogenesis by myostatin activation and myostatin-dependent gene processing in porcine.
authors.affiliation: Department of Animal Biotechnology, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Deng
authors.forename: Shan
authors.initials: S
authors.lastname: Yu
authors.forename: Junlin
authors.initials: J
authors.lastname: Zhang
authors.forename: De
authors.initials: D
authors.lastname: Cheng
authors.forename: Huayan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D004252:DNA Mutational Analysis; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic; D055785:Gene Knockdown Techniques; D064326:MEF2 Transcription Factors; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D055435:Myostatin / Q000235:genetics*; D017384:Sequence Deletion; D034421:Sus scrofa / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D055435:Myostatin