Masuda Takamasa, Ishitani Tohru
Division of Cell Regulation Systems, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
Division of Cell Regulation Systems, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan
J Biochem. 2017 Jan;161(1):9-17. doi: 10.1093/jb/mvw072. Epub 2016 Dec 24.
Wnt/β-catenin signaling is activated repeatedly during an animal's lifespan, and it controls gene expression through its essential nuclear effector, β-catenin, to regulate embryogenesis, organogenesis, and adult homeostasis. Although the β-catenin transcriptional complex has the ability to induce the expression of many genes to exert its diverse roles, it chooses and transactivates a specific gene set from among its numerous target genes depending on the context. For example, the β-catenin transcriptional complex stimulates the expression of cell cycle-related genes and consequent cell proliferation in neural progenitor cells, while it promotes the expression of neural differentiation-related genes in differentiating neurons. Recent studies using animal and cell culture models have gradually improved our understanding of the molecular basis underlying such context-dependent actions of the β-catenin transcriptional complex. Here, we describe eight mechanisms that support β-catenin-mediated context-dependent gene regulation, and their spatio-temporal regulation during vertebrate development. In addition, we discuss their contribution to the diverse functions of Wnt/β-catenin signaling.
Wnt/β-连环蛋白信号在动物的生命周期中会反复被激活，它通过其关键的核效应因子β-连环蛋白来控制基因表达，从而调节胚胎发育、器官形成和成年期的体内平衡。尽管β-连环蛋白转录复合物有能力诱导许多基因的表达以发挥其多样的作用，但它会根据具体情况从众多靶基因中选择并反式激活一组特定的基因。例如，β-连环蛋白转录复合物在神经祖细胞中刺激细胞周期相关基因的表达以及随之而来的细胞增殖，而在分化的神经元中它促进神经分化相关基因的表达。最近使用动物和细胞培养模型的研究逐渐增进了我们对β-连环蛋白转录复合物这种依赖于具体情况的作用背后分子基础的理解。在此，我们描述了支持β-连环蛋白介导的依赖于具体情况的基因调控的八种机制，以及它们在脊椎动物发育过程中的时空调控。此外，我们还讨论了它们对Wnt/β-连环蛋白信号多样功能的贡献。
