Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes
Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes
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DOI：
10.1038/ng1467
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发表时间：
2004-12-01
期刊：
影响因子：
30.8
通讯作者：
Feil, R
中科院分区：
文献类型：
--
作者：
Umlauf, D;Goto, Y;Feil, R
印迹基因在结构域中聚集，并且它们的等位基因抑制由印迹控制区介导（1-3）。这些印记控制区域由DNA甲基化标记，这对维持胚胎中的印记至关重要（4）。为了探索印记是如何在胎盘中调节的，我们研究了小鼠远端7号染色体上的Kcnq 1结构域。该大结构域由内含子印记控制区控制（5，6），并且包含在胎盘中印记的多个基因，而不涉及启动子DNA甲基化（7-10）。我们发现，父系抑制沿着域涉及收购的三甲基化在赖氨酸27和二甲基化在赖氨酸9的组蛋白H3。Eed-Ezh 2 Polycomb复合物被募集到父亲染色体上，并可能调节其抑制性组蛋白甲基化。对胚胎干细胞和早期胚胎的研究支持了我们的观点，即染色质抑制在发育早期就建立起来，并在胎盘中维持。然而，在胚胎中，印记仅在具有启动子DNA甲基化的基因处稳定地维持。这些数据强调了组蛋白甲基化在胎盘印迹中的重要性，并确定了与胚外组织中X染色体失活的机制相似性，表明这两种表观遗传机制在进化上是相关的。
Imprinted genes are clustered in domains, and their allelic repression is mediated by imprinting control regions(1-3). These imprinting control regions are marked by DNA methylation, which is essential to maintain imprinting in the embryo(4). To explore how imprinting is regulated in placenta, we studied the Kcnq1 domain on mouse distal chromosome 7. This large domain is controlled by an intronic imprinting control region(5,6) and comprises multiple genes that are imprinted in placenta, without the involvement of promoter DNA methylation(7-10). We found that the paternal repression along the domain involves acquisition of trimethylation at Lys27 and dimethylation at Lys9 of histone H3. Eed-Ezh2 Polycomb complexes are recruited to the paternal chromosome and potentially regulate its repressive histone methylation. Studies on embryonic stem cells and early embryos support our proposal that chromatin repression is established early in development and is maintained in the placenta. In the embryo, however, imprinting is stably maintained only at genes that have promoter DNA methylation. These data underscore the importance of histone methylation in placental imprinting and identify mechanistic similarities with X-chromosome inactivation in extraembryonic tissues, suggesting that the two epigenetic mechanisms are evolutionarily linked.