Jarid2 结合单泛素化 H2A 赖氨酸 119 以介导多梳复合物 PRC1 和 PRC2 之间的串扰。
Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2.
机构信息
Developmental Epigenetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Institut Curie, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.
出版信息
Nat Commun. 2016 Nov 28;7:13661. doi: 10.1038/ncomms13661.
The Polycomb repressive complexes PRC1 and PRC2 play a central role in developmental gene regulation in multicellular organisms. PRC1 and PRC2 modify chromatin by catalysing histone H2A lysine 119 ubiquitylation (H2AK119u1), and H3 lysine 27 methylation (H3K27me3), respectively. Reciprocal crosstalk between these modifications is critical for the formation of stable Polycomb domains at target gene loci. While the molecular mechanism for recognition of H3K27me3 by PRC1 is well defined, the interaction of PRC2 with H2AK119u1 is poorly understood. Here we demonstrate a critical role for the PRC2 cofactor Jarid2 in mediating the interaction of PRC2 with H2AK119u1. We identify a ubiquitin interaction motif at the amino-terminus of Jarid2, and demonstrate that this domain facilitates PRC2 localization to H2AK119u1 both in vivo and in vitro. Our findings ascribe a critical function to Jarid2 and define a key mechanism that links PRC1 and PRC2 in the establishment of Polycomb domains.
多梳抑制复合物 PRC1 和 PRC2 在多细胞生物的发育基因调控中发挥核心作用。PRC1 和 PRC2 通过催化组蛋白 H2A 赖氨酸 119 泛素化（H2AK119u1）和 H3 赖氨酸 27 甲基化（H3K27me3）分别修饰染色质。这些修饰之间的相互反馈对于靶基因座处稳定多梳域的形成至关重要。虽然 PRC1 识别 H3K27me3 的分子机制已得到很好的定义，但 PRC2 与 H2AK119u1 的相互作用知之甚少。在这里，我们证明了 PRC2 共因子 Jarid2 在介导 PRC2 与 H2AK119u1 的相互作用中起关键作用。我们确定了 Jarid2 氨基末端的一个泛素相互作用基序，并证明该结构域在体内和体外都有助于 PRC2 定位于 H2AK119u1。我们的发现赋予了 Jarid2 关键功能，并定义了一个关键机制，将 PRC1 和 PRC2 联系在一起，以建立多梳域。
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