Dynamics of a developmental switch:: Recursive intracellular and intranuclear redistribution of Caenorhabditis elegans POP-1 parallels Wnt-inhibited transcriptional repression
Dynamics of a developmental switch:: Recursive intracellular and intranuclear redistribution of Caenorhabditis elegans POP-1 parallels Wnt-inhibited transcriptional repression
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DOI：
10.1006/dbio.2002.0721
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发表时间：
2002-08-01
影响因子：
2.7
通讯作者：
Rothman, JH
中科院分区：
文献类型：
--
作者：
Maduro, MF;Lin, RL;Rothman, JH
POP-1是一种Tcf/Lef因子，在秀丽隐杆线虫的整个发育过程中发挥作用，作为Wnt依赖性的反复开关，产生通过前后细胞分裂产生的不等价姐妹细胞。我们已经观察到POP-1和靶基因之间的相互作用，当它响应Wnt信号时，POP-1抑制靶基因。在活胚胎中的动态观察表明，POP-1经历Wnt依赖的核质再分布后立即胞质分裂，解释了差异的核POP-1水平在不等价的姐妹细胞。在无信号（前），但没有Wnt信号（后）的姐妹细胞，POP-1逐步合并成亚核域在间期，符合其作为一个阻遏物的行动。虽然POP-1在非等价姐妹篇中的不对称分布显然需要124个氨基酸的内部结构域，但既不需要HMG盒也不需要β-连环蛋白相互作用结构域。我们发现，转录激活因子，MED-1，在体内与中胚层（前姐妹）和内胚层（后姐妹）的不对称细胞分裂，细分中内胚层的端-1和端-3靶基因。然而，在前姐妹中，POP-1与end-1和end-3基因的结合阻断了它们的表达。在体内，POP-1与末端-1和末端-3靶标（在后姐妹中）的结合被Wnt/MAPK信号传导阻断。因此，Tcf/Lef因子通过废除结合的激活因子的功能来抑制未信号传导的子细胞中基因的反式激活。(C)2002 Elsevier Science（美国）。
POP-1, a Tcf/Lef factor, functions throughout Caenorhabditis elegans development as a Wnt-dependent reiterative switch to generate nonequivalent sister cells that are born by anterior-posterior cell divisions. We have observed the interaction between POP-1 and a target gene that it represses as it responds to Wnt signaling. Dynamic observations in living embryos reveal that POP-1 undergoes Wnt-dependent nucleocytoplasmic redistribution immediately following cytokinesis, explaining the differential nuclear POP-1 levels in nonequivalent sister cells. In unsignaled (anterior) but not Wnt-signaled (posterior) sister cells, POP-1 progressively coalesces into subnuclear domains during interphase, coincident with its action as a repressor. While the asymmetric distribution of POP-1 in nonequivalent sisters apparently requires a 124-amino-acid internal domain, neither the HMG box nor beta-catenin interaction domains are required. We find that a transcriptional activator, MED-1, associates in vivo with the end-1 and end-3 target genes in the mesoderm (anterior sister) and in the endoderm (posterior sister) following the asymmetric cell division that subdivides the mesendoderm. However, in the anterior sister, binding of POP-1 to the end-1 and end-3 genes blocks their expression. In vivo, binding of POP-1 to the end-1 and end-3 targets (in the posterior sister) is blocked by Wnt/MAPK signaling. Thus, a Tcf/Lef factor represses transactivation of genes in an unsignaled daughter cell by abrogating the function of a bound activator. (C) 2002 Elsevier Science (USA).