title: Transcription factor ZBED6 mediates IGF2 gene expression by regulating promoter activity and DNA methylation in myoblasts.
abstract: Zinc finger, BED-type containing 6 (ZBED6) is an important transcription factor in placental mammals, affecting development, cell proliferation and growth. In this study, we found that the expression of the ZBED6 and IGF2 were upregulated during C2C12 differentiation. The IGF2 expression levels were negatively associated with the methylation status in beef cattle (P < 0.05). A luciferase assay for the IGF2 intron 3 and P3 promoter showed that the mutant-type 439 A-SNP-pGL3 in driving reporter gene transcription is significantly higher than that of the wild-type 439 G-SNP-pGL3 construct (P < 0.05). An over-expression assay revealed that ZBED6 regulate IGF2 expression and promote myoblast differentiation. Furthermore, knockdown of ZBED6 led to IGF2 expression change in vitro. Taken together, these results suggest that ZBED6 inhibits IGF2 activity and expression via a G to A transition disrupts the interaction. Thus, we propose that ZBED6 plays a critical role in myogenic differentiation.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling Shaanxi, People's Republic of China.
authors.forename: Yong-Zhen
authors.initials: YZ
authors.lastname: Huang
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling Shaanxi, People's Republic of China.
authors.forename: Liang-Zhi
authors.initials: LZ
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling Shaanxi, People's Republic of China.
authors.forename: Xin-Sheng
authors.initials: XS
authors.lastname: Lai
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling Shaanxi, People's Republic of China.
authors.forename: Ming-Xun
authors.initials: MX
authors.lastname: Li
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling Shaanxi, People's Republic of China.
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Sun
authors.affiliation: United States Department of Agriculture-Agricultural Research Service, Bovine Functional Genomics Laboratory, Beltsville, Maryland, United States of America.
authors.forename: Cong-Jun
authors.initials: CJ
authors.lastname: Li
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling Shaanxi, People's Republic of China.
authors.forename: Xian-Yong
authors.initials: XY
authors.lastname: Lan
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling Shaanxi, People's Republic of China.
authors.forename: Chu-Zhao
authors.initials: CZ
authors.lastname: Lei
authors.affiliation: Institute of Cellular and Molecular Biology, Jiangsu Normal University, Xuzhou Jiangsu, People's Republic of China.
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling Shaanxi, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling Shaanxi, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D002417:Cattle; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D019175:DNA Methylation / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D007438:Introns / Q000235:genetics; D051379:Mice; D032446:Myoblasts / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C513121:IGF2 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C547913:ZBED6 protein, mouse; D007335:Insulin-Like Growth Factor II