Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2.
Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2.
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DOI：
10.1038/ncomms13661
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发表时间：
2016-11-28
影响因子：
16.6
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作者：
Polycomb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分别通过催化组蛋白H2A赖氨酸119泛素化（H2AK119u1）和H3赖氨酸27甲基化（H3K27me3）修饰染色质。这些修饰之间的相互串扰对于在靶基因位点上形成稳定的多梳结构域至关重要。虽然PRC1识别H3K27me3的分子机制已经明确，但PRC2与H2AK119u1的相互作用尚不清楚。在这里，我们证明了PRC2辅助因子Jarid2在介导PRC2与H2AK119u1的相互作用中的关键作用。我们在Jarid2的氨基端发现了一个泛素相互作用基序，并证明该结构域在体内和体外都能促进PRC2定位到H2AK119u1。我们的研究结果归因于Jarid2的关键功能，并定义了在Polycomb结构域建立中连接PRC1和PRC2的关键机制。Polycomb抑制复合物PRC1和PRC2在多细胞生物的基因组发育调控中起着核心作用。在这里，作者描述了PRC2辅助因子Jarid2如何通过与H2AK119u1的相互作用介导PRC2复合体向染色质的募集。
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. The Polycomb repressive complexes PRC1 and PRC2 play a central role in developmental regulation of the genome in multicellular organisms. Here the authors describe how the PRC2 cofactor Jarid2 mediates the recruitment of the PRC2 complex to chromatin via interaction with H2AK119u1.