Polycomb Group Proteins Ezh2 and Rnf2 Direct Genomic Contraction and Imprinted Repression in Early Mouse Embryos
Polycomb Group Proteins Ezh2 and Rnf2 Direct Genomic Contraction and Imprinted Repression in Early Mouse Embryos
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DOI：
10.1016/j.devcel.2008.08.015
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发表时间：
2008-11-11
影响因子：
11.8
通讯作者：
Peters, Antoine H. F. M.
中科院分区：
文献类型：
--
作者：
Terranova, Rrni;Yokobayashi, Shihori;Peters, Antoine H. F. M.
基因组印迹调控特定基因的亲本特异性表达，是哺乳动物正常发育所必需的。然而，印记是如何在开发过程中建立起来的，在很大程度上是未知的。为了解决这个问题，我们研究了小鼠KCNQ1印迹簇，在这个簇上，父系特异性沉默依赖于非编码RNA Kcnq1ot1的表达。我们发现Kcnq1ot1从受精卵阶段开始表达，并迅速与多梳组蛋白(PcG)标记的染色质和抑制性组蛋白修饰结合，形成一个没有RNA聚合酶II的离散的抑制性核室，这种结构也在Igf2r印迹簇中观察到。在这个隔室中，父系KCNQ1簇以三维收缩状态存在。在体内，PcG蛋白Ezh2和Rnf2独立地参与基因组收缩和印迹沉默。我们认为，亲本特异的高阶染色质组织的形成使印迹簇能够单等位基因沉默，并赋予PcG蛋白在这一过程中的中心作用。
Genomic imprinting regulates parental-specific expression of particular genes and is required for normal mammalian development. How imprinting is established during development is, however, largely unknown. To address this question, we studied the mouse Kcnq1 imprinted cluster at which paternal-specific silencing depends on expression of the non-coding RNA Kcnq1ot1. We show that Kcnq1ot1 is expressed from the zygote stage onward and rapidly associates with chromatin marked by Polycomb group (PcG) proteins and repressive histone modifications, forming a discrete repressive nuclear compartment devoid of RNA polymerase II, a configuration also observed at the Igf2r imprinted cluster. In this compartment, the paternal Kcnq1 cluster exists in a three-dimensionally contracted state. In vivo the PcG proteins Ezh2 and Rnf2 are independently required for genomic contraction and imprinted silencing. We propose that the formation of a parental-specific higher-order chromatin organization renders imprint clusters competent for monoallelic silencing and assign a central role to PcG proteins in this process.