Compaction of chromatin by diverse Polycomb group proteins requires localized regions of high charge
Compaction of chromatin by diverse Polycomb group proteins requires localized regions of high charge
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DOI：
10.1101/gad.17288211
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发表时间：
2011-10-15
影响因子：
10.5
通讯作者：
Kingston, Robert E.
中科院分区：
文献类型：
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作者：
Grau, Daniel J.;Chapman, Brad A.;Kingston, Robert E.
Polycomb group（PcG）蛋白是沉默状态下发育基因表观遗传维持所必需的。PcG的多梳抑制复合物1（PRC1）类中的蛋白质从果蝇到人类都是保守的，并抑制转录。PRC1机制的一个假设是它压缩染色质，部分基于电子显微镜实验表明果蝇PRC1压缩核小体阵列。我们发现，这种功能是保守的果蝇和小鼠PRC1复合物之间，需要一个区域与碱性氨基酸的过度表达。虽然在果蝇的后性梳（PSC）亚基中发现了活性区域，但在小鼠中意外地发现了一种不同的PRC1亚基，称为M33的Polycomb同源物。我们提供了一个带电区域的普遍重要性的实验支持，通过预测的PcG蛋白质的压缩能力，从其他物种比果蝇和小鼠，并通过测试这些蛋白质中的几个使用溶液分析和显微镜。我们推断，PcG蛋白质的能力，以紧凑的染色质在体外可以预测的高正电荷的结构域的存在和PRC1组件从各种物种保存这个高电荷区。这支持了压实是PcG功能的关键方面的假设。
Polycomb group (PcG) proteins are required for the epigenetic maintenance of developmental genes in a silent state. Proteins in the Polycomb-repressive complex 1 (PRC1) class of the PcG are conserved from flies to humans and inhibit transcription. One hypothesis for PRC1 mechanism is that it compacts chromatin, based in part on electron microscopy experiments demonstrating that Drosophila PRC1 compacts nucleosomal arrays. We show that this function is conserved between Drosophila and mouse PRC1 complexes and requires a region with an overrepresentation of basic amino acids. While the active region is found in the Posterior Sex Combs (PSC) subunit in Drosophila, it is unexpectedly found in a different PRC1 subunit, a Polycomb homolog called M33, in mice. We provide experimental support for the general importance of a charged region by predicting the compacting capability of PcG proteins from species other than Drosophila and mice and by testing several of these proteins using solution assays and microscopy. We infer that the ability of PcG proteins to compact chromatin in vitro can be predicted by the presence of domains of high positive charge and that PRC1 components from a variety of species conserve this highly charged region. This supports the hypothesis that compaction is a key aspect of PcG function.