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.
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。