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首页> 外文期刊>Molecular and Cellular Biology >Elements of the Polycomb Repressor SU(Z)12 Needed for Histone H3-K27 Methylation, the Interface with E(Z), and In Vivo Function
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Elements of the Polycomb Repressor SU(Z)12 Needed for Histone H3-K27 Methylation, the Interface with E(Z), and In Vivo Function

机译:组蛋白H3-K27甲基化所需的Polycomb Repressor SU(Z)12元素,与E(Z)的界面和体内功能

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Polycomb repressive complex 2 (PRC2) is an essential chromatin-modifying enzyme that implements gene silencing. PRC2 methylates histone H3 on lysine-27 and is conserved from plants to flies to humans. In Drosophila melanogaster, PRC2 contains four core subunits: E(Z), SU(Z)12, ESC, and NURF55. E(Z) bears a SET domain that houses the enzyme active site. However, PRC2 activity depends upon critical inputs from SU(Z)12 and ESC. The stimulatory mechanisms are not understood. We present here functional dissection of the SU(Z)12 subunit. SU(Z)12 contains two highly conserved domains: an ~140-amino-acid VEFS domain and a Cys2-His2 zinc finger (ZnF). Analysis of recombinant PRC2 bearing VEFS domain alterations, including some modeled after leukemia mutations, identifies distinct elements needed for SU(Z)12 assembly with E(Z) and stimulation of histone methyltransferase. The results define an extensive VEFS subdomain that organizes the SU(Z)12-E(Z) interface. Although the SU(Z)12 ZnF is not needed for methyltransferase in vitro, genetic rescue assays show that the ZnF is required in vivo. Chromatin immunoprecipitations reveal that this ZnF facilitates PRC2 binding to a genomic target. This study defines functionally critical SU(Z)12 elements, including key determinants of SU(Z)12-E(Z) communication. Together with recent findings, this illuminates PRC2 modulation by conserved inputs from its noncatalytic subunits.
机译:聚梳抑制复合物2(PRC2)是一种必需的染色质修饰酶,可实现基因沉默。 PRC2使赖氨酸27上的组蛋白H3甲基化,从植物中保存下来就可以飞向人类。在果蝇中,PRC2包含四个核心亚基:E(Z),SU(Z)12,ESC和NURF55。 E(Z)带有一个包含酶活性位点的SET结构域。但是,PRC2的活动取决于SU(Z)12和ESC的关键输入。刺激机制尚不清楚。我们在这里介绍SU(Z)12亚基的功能解剖。 SU(Z)12包含两个高度保守的域:一个〜140个氨基酸的VEFS域和一个Cys 2 -His 2 锌指(ZnF)。带有VEFS域改变的重组PRC2的分析,包括一些在白血病突变后建模的模型,确定了SU(Z)12与E(Z)组装并刺激组蛋白甲基转移酶所需的独特元件。结果定义了一个广泛的VEFS子域,该子域组织了SU(Z)12-E(Z)接口。尽管甲基转移酶在体外不需要SU(Z)12 ZnF,但是基因拯救试验表明,在体内需要ZnF。染色质的免疫沉淀表明,该ZnF促进PRC2与基因组靶标的结合。这项研究定义了功能关键的SU(Z)12元素,包括SU(Z)12-E(Z)通信的关键决定因素。连同最近的发现,这通过其非催化亚基的保守输入阐明了PRC2的调节。

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