Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan.
Nat Commun. 2013;4:1754. doi: 10.1038/ncomms2780.
Embryonic stem cells and primordial germ cells (PGCs) express many pluripotency-associated genes, but embryonic stem cells do not normally undergo conversion into primordial germ cells. Thus, we predicted that there is a mechanism that represses primordial germ cell-related gene expression in embryonic stem cells. Here we identify genes involved in this putative mechanism, by using an embryonic stem cell line with a Vasa reporter in an RNA interference screen of transcription factor genes expressed in embryonic stem cells. We identify five genes that result in the expression of Vasa when silenced. Of these, Max is the most striking. Transcriptome analysis reveals that Max knockdown in embryonic stem cells results in selective, global derepression of germ cell-specific genes. Max interacts with histone H3K9 methyltransferases and associates with the germ cell-specific genes in embryonic stem cells. In addition, Max knockdown results in a decrease in histone H3K9 dimethylation at their promoter regions. We propose that Max is part of protein complex that acts as a repressor of germ cell-related genes in embryonic stem cells.
胚胎干细胞和原始生殖细胞（PGCs）表达许多多能性相关基因，但胚胎干细胞通常不会转化为原始生殖细胞。因此，我们预测在胚胎干细胞中存在一种抑制原始生殖细胞相关基因表达的机制。在这里，我们通过使用在胚胎干细胞中表达的转录因子基因的 RNA 干扰筛选，在带有 Vasa 报告基因的胚胎干细胞系中，鉴定出参与这一假定机制的基因。我们鉴定出了五个在沉默时导致 Vasa 表达的基因。其中，Max 最为显著。转录组分析显示，胚胎干细胞中 Max 的敲低导致生殖细胞特异性基因的选择性、全局去抑制。Max 与组蛋白 H3K9 甲基转移酶相互作用，并与胚胎干细胞中的生殖细胞特异性基因相关联。此外，Max 的敲低导致其启动子区域组蛋白 H3K9 二甲基化减少。我们提出，Max 是在胚胎干细胞中作为生殖细胞相关基因的抑制剂的蛋白复合物的一部分。
