A Maternal Factor Unique to Ascidians Silences the Germline via Binding to P-TEFb and RNAP II Regulation
A Maternal Factor Unique to Ascidians Silences the Germline via Binding to P-TEFb and RNAP II Regulation
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DOI：
10.1016/j.cub.2011.06.050
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发表时间：
2011-08-09
期刊：
影响因子：
9.2
通讯作者：
Nishida, Hiroki
中科院分区：
文献类型：
--
作者：
Kumano, Gaku;Takatori, Naohito;Nishida, Hiroki
早期胚胎生殖系细胞中合子转录的抑制与它们与体细胞谱系的分离密切相关。许多无脊椎动物胚胎利用由种系细胞连续遗传的局部母系因子来沉默种系细胞。种系静止也与RNA聚合酶II c端结构域（CTD-Ser2）的Ser2磷酸化不足有关[1-3]。在这里，使用海鞘Halocynthia roretzi，我们发现了一个母系定位因子的第一个后口例子，后端标记（PEM），它在全局上抑制种系转录。PEM敲低导致种系CTD-Ser2的异位转录和异位磷酸化。PEM的过表达消除了体细胞中所有的转录并导致CTD-Ser2的低磷酸化。PEM蛋白在种系细胞核中反复检测到，并与CDK9共免疫沉淀，CDK9是后转录延伸因子b （P-TEFb）的一个组成部分。这些结果表明，非同源蛋白，果蝇的PEM和Pgc[3-5]和秀丽隐杆线虫的py -1[1,6,7]，通过类似的功能抑制种系基因表达：通过结合P-TEFb复合物保持CTD-Ser2的低磷酸化。目前的研究是进化限制的一个有趣的例子，关于种系沉默机制如何在不同的动物中进化。
Suppression of zygotic transcription in early embryonic germline cells is tightly linked to their separation from the somatic lineage. Many invertebrate embryos utilize localized maternal factors that are successively inherited by the germline cells for silencing the germline. Germ line quiescence has also been associated with the underphosphorylation of Ser2 of the C-terminal domain (CTD-Ser2) of RNA polymerase II [1-3]. Here, using the ascidian Halocynthia roretzi, we identified a first deuterostome example of a maternally localized factor, posterior end mark (PEM), which globally represses germline transcription. PEM knockdown resulted in ectopic transcription and ectopic phosphorylation of CTD-Ser2 in the germline. Overexpression of PEM abolished all transcription and led to the underphosphorylation of CTD-Ser2 in the somatic cells. PEM protein was reiteratively detected in the nucleus of the germline cells and coimmunoprecipitated with CDK9, a component of posterior transcription elongation factor b (P-TEFb). These results suggest that nonhomologous proteins, PEM and Pgc of Drosophila [3-5] and PIE-1 of C. elegans [1, 6, 7], repress germline gene expression through analogous functions: by keeping CTD-Ser2 underphosphorylated through binding to the P-TEFb complex. The present study is an interesting example of evolutionary constraint on how a mechanism of germline silencing can evolve in diverse animals.