Omoteyama Kazuki, Mikami Yoshikazu, Takagi Minoru
Department of Anatomy, Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, 1-8-13, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
Biochem Biophys Res Commun. 2007 Jul 6;358(3):885-9. doi: 10.1016/j.bbrc.2007.05.009. Epub 2007 May 8.
The Fox family of transcription factors is expressed in various organs and tissues during development, and is involved in a variety of developmental and cellular differentiation processes. Foxc2 mRNA is strongly expressed in mesoderm-derived tissues in the embryo, but the molecular mechanism of Foxc2-induced cellular differentiation and the physiological role of Foxc2 are unclear. In mouse myoblast C2C12 cells, over-expression of Foxc2 increased the expression of desmin, the muscle-specific member of the intermediate filament family of proteins, and induced the synthesis of myotubes. Transient expression of Foxc2 increased MyoD mRNA and protein levels, as assessed by real-time PCR and Western blot, respectively. Chromatin immunoprecipitation (ChIP) analysis showed that Foxc2 does not bind to the promoter region of the MyoD gene, which indicated that Foxc2 does not directly activate MyoD. In contrast to reports that Foxc2 regulates the production of basement membrane components in endothelial cells, we found no evidence of Foxc2-mediated regulation of Collagen type IV alpha 1 (Col4a1) or Col4a2 in myoblast cells. Taken together, these results indicate that Foxc2 plays an important role in the development of the mesenchyme through the regulation of MyoD gene expression.
转录因子Fox家族在发育过程中在各种器官和组织中表达，并参与多种发育和细胞分化过程。Foxc2 mRNA在胚胎中胚层来源的组织中强烈表达，但Foxc2诱导细胞分化的分子机制以及Foxc2的生理作用尚不清楚。在小鼠成肌细胞C2C12细胞中，Foxc2的过表达增加了结蛋白（中间丝蛋白家族的肌肉特异性成员）的表达，并诱导了肌管的合成。通过实时PCR和蛋白质印迹分别评估，Foxc2的瞬时表达增加了MyoD mRNA和蛋白质水平。染色质免疫沉淀（ChIP）分析表明，Foxc2不与MyoD基因的启动子区域结合，这表明Foxc2不直接激活MyoD。与Foxc2调节内皮细胞中基底膜成分产生的报道相反，我们没有发现Foxc2介导的成肌细胞中IV型胶原α1（Col4a1）或Col4a2调节的证据。综上所述，这些结果表明Foxc2通过调节MyoD基因表达在间充质发育中起重要作用。
