MRG-1 is required for both chromatin-based transcriptional silencing and genomic integrity of primordial germ cells in C. elegans.
MRG-1 is required for both chromatin-based transcriptional silencing and genomic integrity of primordial germ cells in C. elegans.
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MRG-1 是线虫原始生殖细胞基于染色质的转录沉默和基因组完整性所必需的。
作者：
Miwa;T.;Inoue;K.;Sakamoto;H.
在秀丽隐杆线虫中，生殖系细胞在胚胎发生过程中保持转录沉默。转录沉默通过两种不同的机制实现：一种是在P2‐P4细胞建立阶段抑制RNA聚合酶II，另一种是在两个原始生殖细胞（PGCs）的维持阶段基于染色质的沉默；然而，基于染色质的沉默的分子机制尚不清楚。我们研究了染色体结构域蛋白MRG‐1在PGCs转录沉默中的作用，MRG‐1是种系发育的重要母体因子。缺乏母体MRG‐1的PGCs表现出两种组蛋白修饰（H3K4me2和H4K16ac）水平升高，这两种组蛋白修饰是活性转录和种系启动子过早激活的表观遗传标记。H3K36甲基转移酶MES‐4的缺失也会导致PGCs中生殖系基因的类似下调，这表明MRG‐1和MES‐4在PGCs中基于染色质的沉默中都起作用。此外，mrg‐1null突变体在PGCs中表现出异常的染色体结构和同源重组酶RAD‐51位点的减少，但themes‐4null突变体没有表现出这种表型。综上所述，我们认为MRG‐1具有两种不同的功能：基于染色质的转录沉默和在PGCs维持阶段保持基因组完整性。
InCaenorhabditis elegans, germline cells remain transcriptionally silenced during embryogenesis. The transcriptional silencing is achieved by two different mechanisms: One is the inhibition of RNA polymerase II in P2‐P4 cells at the establishment stage, and another is chromatin‐based silencing in two primordial germ cells (PGCs) at the maintenance stage; however, the molecular mechanism underlying chromatin‐based silencing is less understood. We investigated the role of the chromodomain protein MRG‐1, which is an essential maternal factor for germline development, in transcriptional silencing in PGCs. PGCs lacking maternal MRG‐1 showed increased levels of two histone modifications (H3K4me2 and H4K16ac), which are epigenetic markers for active transcription, and precocious activation of germline promoters. Loss of MES‐4, a H3K36 methyltransferase, also caused similar derepression of the germline genes in PGCs, suggesting that both MRG‐1 and MES‐4 function in chromatin‐based silencing in PGCs. In addition, themrg‐1null mutant showed abnormal chromosome structures and a decrease in homologous recombinase RAD‐51 foci in PGCs, but themes‐4null mutant did not show such phenotypes. Taken together, we propose that MRG‐1 has two distinct functions: chromatin‐based transcriptional silencing and preserving genomic integrity at the maintenance stage of PGCs.