The Laboratory of Cell and Development, Northeast Agricultural University, XiangFang District, Harbin, Heilongjiang Province, China.
Department of Life Science and Agroforestry, Qiqihar University, JianHua District, Qiqihar, Heilongjiang Province, China.
J Cell Physiol. 2018 Jan;233(1):350-362. doi: 10.1002/jcp.25883. Epub 2017 May 18.
The transcription factor, early growth response 1 (EGR1), has important roles in various cell types in response to different stimuli. EGR1 is thought to be involved in differentiation of bovine skeletal muscle-derived satellite cells (MDSCs); however, the precise effects of EGR1 on differentiation of MDSCs and its mechanism of action remain unknown. In the present study, a time course of EGR1 expression and the effects of EGR1 on MDSC differentiation were determined. The results demonstrated that the expression of EGR1 mRNA and protein increased significantly in differentiating MDSCs relative to that in proliferating cells. Over-expression of the EGR1 gene in MDSCs promoted their differentiation and inhibited proliferation. Conversely, knock-down of EGR1 inhibited differentiation of MDSCs and promoted their proliferation, indicating that EGR1 promotes MDSC differentiation. Moreover, over-expression of EGR1 in MDSCs increased the expression of MyoG mRNA and protein, whereas its knock-down had the opposite effect. Furthermore, ChIP-PCR analyses demonstrated that EGR1 could bind directly to its putative binding site within the promoter region of MyoG, and determination of ERG1 subcellular localization in MDSCs demonstrated that it could relocate to the nucleus, indicating MyoG is likely an EGR1 target gene whose expression is positively regulated by this transcription factor. In conclusion, EGR1 can promote MDSC differentiation through positive regulation of MyoG gene expression.
转录因子早期生长反应因子 1(EGR1)在各种细胞类型中对不同刺激的反应中具有重要作用。EGR1 被认为参与了牛骨骼肌卫星细胞(MDSCs)的分化;然而,EGR1 对 MDSCs 分化的确切影响及其作用机制尚不清楚。在本研究中,确定了 EGR1 表达的时间进程以及 EGR1 对 MDSC 分化的影响。结果表明,与增殖细胞相比,分化中的 MDSC 中 EGR1 mRNA 和蛋白的表达显著增加。EGR1 基因在 MDSC 中的过表达促进了其分化并抑制了增殖。相反,EGR1 的敲低抑制了 MDSC 的分化并促进了其增殖,表明 EGR1 促进 MDSC 分化。此外,在 MDSC 中过表达 EGR1 增加了 MyoG mRNA 和蛋白的表达,而敲低 EGR1 则产生相反的效果。此外,ChIP-PCR 分析表明,EGR1 可以直接与其假定的 MyoG 启动子区域内的结合位点结合,并且在 MDSC 中确定 EGR1 的亚细胞定位表明它可以重新定位到细胞核,表明 MyoG 可能是 EGR1 的靶基因,其表达受到该转录因子的正向调控。总之,EGR1 可以通过 MyoG 基因表达的正向调节来促进 MDSC 分化。