Analysis of the mrg-1 gene function required for differentiation of primordial germ cells in the nematode C.elegans

生殖细胞是唯一能够产生下一代的细胞，因此对物种的永久存在负有责任。在许多动物中，原始生殖细胞(PGC)的建立取决于几个母体因素。然而，关于母系因素如何赋予生殖细胞特殊属性的分子机制，目前还知之甚少。我们在这里表明，母体需要一个色域蛋白MRG-1来启动生殖系特异性基因PGL-1的表达。MRG-1定位于细胞核并与染色体相关，提示MRG-1通过染色质重塑调节生殖系特异基因的转录活性。先前的研究表明，在缺乏MEP-1的动物的体细胞中，生殖系特异性基因会被去抑制，MEP-1是核小体重塑和组蛋白脱乙酰酶(NuRD)复合体的一个组成部分(1)。我们发现，MRG-1的缺失抑制了MEP-1的表型：体细胞中生殖系特异基因的异位表达。这些研究表明，MRG-1具有在母体中向所有卵裂球表达Gemline特异性基因的潜力，并且其活性受MRG-1和MEP-1之间的相互作用限制在PGCs中。据报道，MEP-1的表型也受到MES-2、MES-3、MES-4和MES-6基因突变的抑制。MES蛋白被证明在组蛋白甲基化中起作用。虽然MRG-1的无菌表型和表达模式与MES基因非常相似，但MRG-1的突变并不影响MES蛋白的定位模式或组蛋白甲基转移酶的活性。这些结果表明，MRG-1与MES蛋白在下游或平行发挥作用。我们的发现支持一个模型，在这个模型中，几个母系因子积累在PGCs的细胞核中，发挥重要作用，共同作用，确保生殖系特异基因的转录活性，至少部分通过染色质重塑。

Germ cells are the only cells that can give rise to next generation and thus are responsible for perpetuation of species. In many animals, establishment of the primordial germ cell (PGC) depends on several maternal factors. However, little is known about the molecular mechanism how maternal factors give the special property of germ cells to PGCs. We show here that a chromodomain protein MRG-1 is required maternally for PGCs to initiate expression of the germline-specific gene pgl-1. MRG-1 is localized to nuclei and associated with chromosomes, suggesting that MRG-1 regulates transcriptional activity of germline-specific genes through chromatin remodeling. Previous study revealed that germline-specific genes become derepressed in somatic cells in animals lacking MEP-1, which is a component of the nucleosome remodeling and histone deacetylase (NuRD) complex (1). We found that depletion of MRG-1 suppresses the Mep-1 phenotype : ectopic expression of germline-specific genes in somatic cells. These studies suggest that MRG-1 gives maternally the potential to express gemline-specific genes to all blastomeres, and the activity is restricted to PGCs by the interaction between MRG-1 and MEP-1. It has been reported that Mep-1 phenotype is also suppressed by mutations in mes-2, mes-3, mes-4 and mes-6 genes. MES proteins are shown to function in histone methylation. Although the sterile phenotype and expression pattern of mrg-1 is quite similar to those of mes genes, mutations in mrg-1 do not affect the localization pattern or the histone methyltransferase activities of MES proteins. These results suggest that MRG-1 acts downstream or parallel with MES proteins. Our findings support a model in which several maternal factors accumulated in the nuclei of PGCs are play an important role to act together to ensure the transcriptional activity of germline-specific genes, at least in part, through chromatin remodeling.