Maternally expressed NLRP2 links the subcortical maternal complex (SCMC) to fertility, embryogenesis and epigenetic reprogramming.
Maternally expressed NLRP2 links the subcortical maternal complex (SCMC) to fertility, embryogenesis and epigenetic reprogramming.
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DOI：
10.1038/srep44667
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发表时间：
2017-03-20
影响因子：
4.6
通讯作者：
Van den Veyver IB
中科院分区：
文献类型：
--
作者：
Mahadevan S;Sathappan V;Utama B;Lorenzo I;Kaskar K;Van den Veyver IB
哺乳动物亲本基因组对早期胚胎发育的贡献不同。在合子基因组激活之前，母体基因组提供从高度特化的卵母细胞向多能胚胎转变所需的所有转录物和蛋白质。这些母体编码的转录物的缺失经常导致植入前胚胎发育的失败，但它们在这一过程中的功能还不完全清楚。我们发现，缺乏NLRP 2的雌性小鼠生育能力低下，因为早期胚胎丢失和产生较少的后代，这些后代具有广泛的发育表型和印记基因座处的异常DNA甲基化。通过证明NLRP 2是皮质下母体复合体（SCMC）的成员，SCMC是卵母细胞和植入前胚胎中一种重要的细胞质复合体，其功能知之甚少，我们确定了印迹的合子后DNA甲基化维持，可能是通过指导参与这一过程的蛋白质（如DNMT 1）的亚细胞定位，作为SCMC对哺乳动物生殖的一个新的关键作用。
Mammalian parental genomes contribute differently to early embryonic development. Before activation of the zygotic genome, the maternal genome provides all transcripts and proteins required for the transition from a highly specialized oocyte to a pluripotent embryo. Depletion of these maternally-encoded transcripts frequently results in failure of preimplantation embryonic development, but their functions in this process are incompletely understood. We found that female mice lacking NLRP2 are subfertile because of early embryonic loss and the production of fewer offspring that have a wide array of developmental phenotypes and abnormal DNA methylation at imprinted loci. By demonstrating that NLRP2 is a member of the subcortical maternal complex (SCMC), an essential cytoplasmic complex in oocytes and preimplantation embryos with poorly understood function, we identified imprinted postzygotic DNA methylation maintenance, likely by directing subcellular localization of proteins involved in this process, such as DNMT1, as a new crucial role of the SCMC for mammalian reproduction.