Maternal Eed knockout causes loss of H3K27me3 imprinting and random X inactivation in the extraembryonic cells.
Maternal Eed knockout causes loss of H3K27me3 imprinting and random X inactivation in the extraembryonic cells.
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DOI：
10.1101/gad.318675.118
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发表时间：
2018-12-01
影响因子：
10.5
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Inoue A;Chen Z;Yin Q;Zhang Y
在这项研究中，井上等人。研究了母体H3K27me3机制的调控机制和功能。他们发现，母体EED是多梳基复合体2(PRC2)的重要组成部分，是建立H3K27me3印迹所必需的，他们的结果也揭示了在没有Xist印迹的情况下独特的XCI动力学。基因组印记对于哺乳动物的发育是必不可少的。最近的研究表明，母体组蛋白H3Lys27三甲基化(H3K27me3)可以介导DNA甲基化非依赖的基因组印迹。然而，这种新的印迹机制的调节机制和功能在很大程度上是未知的。在这里，我们证明了母体EED是多梳基复合体2(PRC2)的重要组成部分，是建立H3K27me3印迹所必需的。我们发现，包括Xist在内的所有H3K27me3印记基因在Eed母体基因敲除(Matko)胚胎中都失去了印记表达，导致了男性偏见的致死率。令人惊讶的是，尽管由于Xist印记的丢失，Eed Matko胚胎在植入前会发生母体X染色体失活(XmCI)，但在围着床期它会得到解决。最终，在随机XCI之前，两条X染色体在胚胎细胞谱系中都被重新激活，而在胚外细胞谱系中，只有一条X染色体经历了随机XCI。因此，我们的研究不仅证明了Eed在H3K27me3印迹建立中的重要作用，而且还揭示了在没有Xist印迹的情况下一种独特的XCI动态。
In this study, Inoue et al. investigated the regulatory mechanisms and functions of the maternal H3K27me3 mechanism. They found that maternal Eed, an essential component of the Polycomb group complex 2 (PRC2), is required for establishing H3K27me3 imprinting, and their results also reveal unique XCI dynamics in the absence of Xist imprinting. Genomic imprinting is essential for mammalian development. Recent studies have revealed that maternal histone H3 Lys27 trimethylation (H3K27me3) can mediate DNA methylation-independent genomic imprinting. However, the regulatory mechanisms and functions of this new imprinting mechanism are largely unknown. Here we demonstrate that maternal Eed, an essential component of the Polycomb group complex 2 (PRC2), is required for establishing H3K27me3 imprinting. We found that all H3K27me3-imprinted genes, including Xist, lose their imprinted expression in Eed maternal knockout (matKO) embryos, resulting in male-biased lethality. Surprisingly, although maternal X-chromosome inactivation (XmCI) occurs in Eed matKO embryos at preimplantation due to loss of Xist imprinting, it is resolved at peri-implantation. Ultimately, both X chromosomes are reactivated in the embryonic cell lineage prior to random XCI, and only a single X chromosome undergoes random XCI in the extraembryonic cell lineage. Thus, our study not only demonstrates an essential role of Eed in H3K27me3 imprinting establishment but also reveals a unique XCI dynamic in the absence of Xist imprinting.
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DOI：
10.1126/science.aal2512
发表时间：
2017-06-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Almeida M;Pintacuda G;Masui O;Koseki Y;Gdula M;Cerase A;Brown D;Mould A;Innocent C;Nakayama M;Schermelleh L;Nesterova TB;Koseki H;Brockdorff N
通讯作者：
Brockdorff N
影响因子：
16.8
作者：
Borensztein M;Syx L;Ancelin K;Diabangouaya P;Picard C;Liu T;Liang JB;Vassilev I;Galupa R;Servant N;Barillot E;Surani A;Chen CJ;Heard E
通讯作者：
Heard E
影响因子：
29
作者：
Donovan, A;Lima, CA;Andrews, NC
通讯作者：
Andrews, NC
影响因子：
56.9
作者：
Bourc'his, D;Xu, GL;Bestor, TH
通讯作者：
Bestor, TH
影响因子：
64.5
作者：
Jonkers, Iris;Barakat, Tahsin Stefan;Gribnau, Joost
通讯作者：
Gribnau, Joost