Submitted to: Scientific Reports
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/18/2014
Publication Date: 4/2/2014
Citation: Young-Zhen, H., Liangzhi, Z., Xin-Sheng, L., Yu-Jia, S., Li, C., Xian-Yong, L., Chu-Zhao, L., Chun-Lei, Z., Xin, Z., Hong, C. 2014. Transcription factor ZBED6 mediates IGF2 gene expression by regulating promoter activity and DNA methylation in myoblasts. Scientific Reports. 4:4570. DOI:10.1038/srep04570. Interpretive Summary: IGF2 is a very important gene that regulates animal development. IGF2 expression is tightly controlled. However, the mechanisms that control IGF2 expression are not clear yet. This study found that a transcription factor ZBED6 can inhibit IGF2 expression, therefore regulating the IGF2 expression. This study suggests that ZBED6 plays a critical role in animal development. This study helps us to understand the mechanisms of animal growth regulation.
Technical 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 up regulated 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 439 G-SNP-pGL3 in driving reporter gene transcription is significantly higher than that of the 439 A-SNP-pGL3 construct (P < 0.05). An over-expression assay revealed that ZBED6 regulates IGF2 expression and promotes myoblast differentiation. Furthermore, knockdown of ZBED6 led to IGF2 expression changes in vitro. These results suggest that ZBED6 inhibits IGF2 activity and expression via a G to A transition at the region of the basal promoter of bovine IGF2. Thus we propose that ZBED6 plays a critical role in myogenic differentiation.