Xiong Zhenzhen, Wang Mengni, You Shanshan, Chen Xiaoyan, Lin Jiangguo, Wu Jianhua, Shi Xiaozhong
School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.
Research Department of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Biology (Basel). 2022 Mar 16;11(3):446. doi: 10.3390/biology11030446.
has been identified as a direct, downstream target gene of MRF in the skeletal muscle. The overexpression of represses myogenic proliferation and promotes cell differentiation. Previous studies have defined the 0.7 kb upstream fragment of the gene. In the present study, we have further determined two clusters of transcription factor-binding motifs in the 0.7 kb promoter: CRE#2-E#1-CRE#1 in the proximal region and Mef2#3-CRE#3-E#4 in the distal region. Utilizing transcription assays, we have also shown that the reporter containing the Mef2#3-CRE#3-E#4 motifs is synergistically transactivated by Mef2c and Creb1. Further studies have mapped out the protein-protein interaction between Mef2c and Creb1. In summary, our present studies support the notion that the triple complex of Mef2c, Creb1 and Myod interacts with the Mef2#3-CRE#3-E#4 motifs in the distal region of the promoter, thereby driving expression during skeletal muscle development and regeneration.
已被确定为骨骼肌中MRF的直接下游靶基因。该基因的过表达抑制肌源性增殖并促进细胞分化。先前的研究已确定了该基因0.7 kb的上游片段。在本研究中，我们进一步确定了0.7 kb启动子中的两个转录因子结合基序簇：近端区域的CRE#2-E#1-CRE#1和远端区域的Mef2#3-CRE#3-E#4。利用转录分析，我们还表明含有Mef2#3-CRE#3-E#4基序的报告基因被Mef2c和Creb1协同反式激活。进一步的研究已经确定了Mef2c和Creb1之间的蛋白质-蛋白质相互作用。总之，我们目前的研究支持这样一种观点，即Mef2c、Creb1和Myod的三元复合物与该基因启动子远端区域的Mef2#3-CRE#3-E#4基序相互作用，从而在骨骼肌发育和再生过程中驱动该基因的表达。
