PDF(Pubmed)
Abstract：
BACKGROUND: Genome-wide DNA demethylation occurs in mammalian primordial germ cells (PGCs) as part of the epigenetic reprogramming important for gametogenesis and resetting the epigenetic information for totipotency. Dppa3 (also known as Stella or Pgc7) is highly expressed in mouse PGCs and oocytes and encodes a factor essential for female fertility. It prevents excessive DNA methylation in oocytes and ensures proper gene expression in preimplantation embryos: however, its role in PGCs is largely unexplored. In the present study, we investigated whether or not DPPA3 has an impact on CG methylation/demethylation in mouse PGCs.
RESULTS: We show that DPPA3 plays a role in genome-wide demethylation in PGCs even before sex differentiation. Dppa3 knockout female PGCs show aberrant hypermethylation, most predominantly at H3K9me3-marked retrotransposons, which persists up to the fully-grown oocyte stage. DPPA3 works downstream of PRDM14, a master regulator of epigenetic reprogramming in embryonic stem cells and PGCs, and independently of TET1, an enzyme that hydroxylates 5-methylcytosine.
CONCLUSIONS: The results suggest that DPPA3 facilitates DNA demethylation through a replication-coupled passive mechanism in PGCs. Our study identifies DPPA3 as a novel epigenetic reprogramming factor in mouse PGCs.
RESULTS: We show that DPPA3 plays a role in genome-wide demethylation in PGCs even before sex differentiation. Dppa3 knockout female PGCs show aberrant hypermethylation, most predominantly at H3K9me3-marked retrotransposons, which persists up to the fully-grown oocyte stage. DPPA3 works downstream of PRDM14, a master regulator of epigenetic reprogramming in embryonic stem cells and PGCs, and independently of TET1, an enzyme that hydroxylates 5-methylcytosine.
CONCLUSIONS: The results suggest that DPPA3 facilitates DNA demethylation through a replication-coupled passive mechanism in PGCs. Our study identifies DPPA3 as a novel epigenetic reprogramming factor in mouse PGCs.
摘要：
背景：全基因组DNA去甲基化发生在哺乳动物原始生殖细胞（PGCs）中，作为表观遗传重编程的一部分，对于配子发生和重置表观遗传信息以获得全能性很重要。Dppa3（也称为Stella或Pgc7）在小鼠PGCs和卵母细胞中高度表达，并编码雌性生育力必需的因子。它可以防止卵母细胞中过度的DNA甲基化，并确保在植入前胚胎中正确的基因表达：其在PGCs中的作用在很大程度上尚未被探索。在本研究中,我们研究了DPPA3是否对小鼠PGCs的CG甲基化/去甲基化有影响.
结果：我们表明DPPA3在PGCs的全基因组去甲基化中起作用，甚至在性别分化之前。Dppa3敲除的雌性PGCs显示异常超甲基化，最主要的是H3K9me3标记的反转录转座子，持续到完全生长的卵母细胞阶段。DPPA3在PRDM14的下游工作，PRDM14是胚胎干细胞和PGCs中表观遗传重编程的主要调节因子，并且独立于TET1，一种羟基化5-甲基胞嘧啶的酶。
结论：结果表明DPPA3通过PGC中的复制偶联被动机制促进DNA去甲基化。我们的研究将DPPA3确定为小鼠PGCs中的新型表观遗传重编程因子。
结果：我们表明DPPA3在PGCs的全基因组去甲基化中起作用，甚至在性别分化之前。Dppa3敲除的雌性PGCs显示异常超甲基化，最主要的是H3K9me3标记的反转录转座子，持续到完全生长的卵母细胞阶段。DPPA3在PRDM14的下游工作，PRDM14是胚胎干细胞和PGCs中表观遗传重编程的主要调节因子，并且独立于TET1，一种羟基化5-甲基胞嘧啶的酶。
结论：结果表明DPPA3通过PGC中的复制偶联被动机制促进DNA去甲基化。我们的研究将DPPA3确定为小鼠PGCs中的新型表观遗传重编程因子。
