DNA methylation is a repressive epigenetic modification that is essential for development and its disruption is widely implicated in disease. Yet, remarkably, ablation of DNA methylation in transgenic mouse models has limited impact on transcriptional states. Across multiple tissues and developmental contexts, the predominant transcriptional signature upon loss of DNA methylation is the de-repression of a subset of germline genes, normally expressed in gametogenesis. We recently reported loss of de novo DNA methyltransferase DNMT3B resulted in up-regulation of germline genes and impaired syncytiotrophoblast formation in the murine placenta. This defect led to embryonic lethality. We hypothesize that de-repression of germline genes in the Dnmt3b knockout underpins aspects of the placental phenotype by interfering with normal developmental processes. Specifically, we discuss molecular mechanisms by which aberrant expression of the piRNA pathway, meiotic proteins or germline transcriptional regulators may disrupt syncytiotrophoblast development.

中文翻译：

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DNA 甲基化缺失会扰乱合体滋养层发育：异常种系基因激活的拟议后果

DNA 甲基化是一种抑制性表观遗传修饰，对于发育至关重要，其破坏与疾病广泛相关。然而，值得注意的是，转基因小鼠模型中 DNA 甲基化的消除对转录状态的影响有限。在多个组织和发育环境中，DNA 甲基化缺失后的主要转录特征是通常在配子发生中表达的生殖系基因子集的去抑制。我们最近报道了从头 DNA 甲基转移酶 DNMT3B 的缺失导致小鼠胎盘中种系基因的上调和合体滋养层形成受损。这种缺陷导致胚胎死亡。我们假设Dnmt3b敲除中种系基因的去抑制通过干扰正常发育过程来支撑胎盘表型的各个方面。具体来说，我们讨论了 piRNA 途径、减数分裂蛋白或种系转录调节因子的异常表达可能破坏合体滋养层发育的分子机制。