Transcriptional repression and DNA hypermethylation of a small set of ES cell marker genes in male germline stem cells.
Transcriptional repression and DNA hypermethylation of a small set of ES cell marker genes in male germline stem cells.
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DOI：
10.1186/1471-213x-6-34
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发表时间：
2006-07-21
影响因子：
--
通讯作者：
Yamanaka S
中科院分区：
文献类型：
--
作者：
Imamura M;Miura K;Iwabuchi K;Ichisaka T;Nakagawa M;Lee J;Kanatsu-Shinohara M;Shinohara T;Yamanaka S
我们之前发现了一组被称为ECAT(ES细胞相关转录本)的基因，它们在小鼠ES细胞中高水平表达。在这里，我们研究了ECAT在体细胞和生殖细胞中的表达和DNA甲基化。在所检测的所有ECAT中，启动子区在ES细胞中的甲基化水平较低，但在体细胞中的甲基化水平较高。相比之下，尽管雄性生殖系干细胞(GS)缺乏多能性，但它们表达大多数ECAT，并显示ECAT启动子区域的低甲基化。我们在成人睾丸和分离的精子中观察到类似的ECAT基因低甲基化。一些ECAT在雄性生殖细胞中的甲基化程度甚至比在ES细胞中更低。然而，少数ECAT在GS细胞中不表达，大多数ECAT是Oct3/4和Sox2的靶标。在这些基因中，八聚体/SOX调节元件发生了高甲基化。此外，我们还发现GS细胞在其转录产物中大量表达Sox2蛋白和低Oct3/4蛋白。我们的结果表明，一小部分ECAT的DNA超甲基化和转录抑制，以及Oct3/4和Sox2的转录后抑制，导致了雄性生殖细胞多能性的丧失。
We previously identified a set of genes called ECATs (ES cell-associated transcripts) that are expressed at high levels in mouse ES cells. Here, we examine the expression and DNA methylation of ECATs in somatic cells and germ cells. In all ECATs examined, the promoter region had low methylation levels in ES cells, but higher levels in somatic cells. In contrast, in spite of their lack of pluripotency, male germline stem (GS) cells expressed most ECATs and exhibited hypomethylation of ECAT promoter regions. We observed a similar hypomethylation of ECAT loci in adult testis and isolated sperm. Some ECATs were even less methylated in male germ cells than in ES cells. However, a few ECATs were not expressed in GS cells, and most of them targets of Oct3/4 and Sox2. The Octamer/Sox regulatory elements were hypermethylated in these genes. In addition, we found that GS cells express little Sox2 protein and low Oct3/4 protein despite abundant expression of their transcripts. Our results suggest that DNA hypermethylation and transcriptional repression of a small set of ECATs, together with post-transcriptional repression of Oct3/4 and Sox2, contribute to the loss of pluripotency in male germ cells.