A core subunit of Polycomb repressive complex 1 is broadly conserved in function but not primary sequence
A core subunit of Polycomb repressive complex 1 is broadly conserved in function but not primary sequence
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DOI：
10.1073/pnas.1118678109
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发表时间：
2012-05-01
影响因子：
11.1
通讯作者：
Francis, Nicole J.
中科院分区：
文献类型：
--
作者：
Beh, Leslie Y.;Colwell, Lucy J.;Francis, Nicole J.
PcG蛋白通过改变染色质结构来介导可遗传的基因沉默。一种重要的PcG复合体，Prc1，压缩染色质并抑制染色质重塑。在果蝇中，PSC的C端无序区域(PSC-CTR)介导染色质的这些非共价效应，是生存所必需的。由于PSC-CTR序列的保守性很差，其对果蝇外染色质的影响的意义尚不清楚。折叠结构域的缺失也使得人们很难理解PSC-CTR序列是如何编码其功能的。为了确定PSC-CTR活性保持的机制基础和程度，我们鉴定了17个从脊索动物到节肢动物的后生动物PSC-CTR，并检测了它们的序列特征和生化性质。PSC-CTR序列保守性差，但都是高度带电的，结构无序。我们表明，活性的PSC-CTR-它紧密结合DNA并有效地抑制染色质重塑-由于没有延长的负电荷伸展，所以与活性较低的PSC-CTR不同。PSC-CTR的活性可以通过分散其连续的负电荷来提高，证实了这一性质的重要性。使用被定义为对PSC-CTR活性重要的序列属性，我们预测在其他不同的基因组中存在活性的PSC-CTR。我们的分析显示PSC-CTR活性在后生动物中具有广泛的保守性。这一结论不可能从序列比对中确定。我们进一步发现，缺乏活性PSC-CTR的植物反而拥有功能类似的PcG蛋白EMF1。因此，我们的研究表明，PRC1活性背后有一个带有分散负电荷的无序结构域，并且在后生动物和植物中是保守的。
Polycomb Group (PcG) proteins mediate heritable gene silencing by modifying chromatin structure. An essential PcG complex, PRC1, compacts chromatin and inhibits chromatin remodeling. In Drosophila melanogaster, the intrinsically disordered C-terminal region of PSC (PSC-CTR) mediates these noncovalent effects on chromatin, and is essential for viability. Because the PSC-CTR sequence is poorly conserved, the significance of its effects on chromatin outside of Drosophila was unclear. The absence of folded domains also made it difficult to understand how the sequence of PSC-CTR encodes its function. To determine the mechanistic basis and extent of conservation of PSC-CTR activity, we identified 17 metazoan PSC-CTRs spanning chordates to arthropods, and examined their sequence features and biochemical properties. PSC-CTR sequences are poorly conserved, but are all highly charged and structurally disordered. We show that active PSC-CTRs-which bind DNA tightly and inhibit chromatin remodeling efficiently-are distinguished from less active ones by the absence of extended negatively charged stretches. PSC-CTR activity can be increased by dispersing its contiguous negative charge, confirming the importance of this property. Using the sequence properties defined as important for PSC-CTR activity, we predicted the presence of active PSC-CTRs in additional diverse genomes. Our analysis reveals broad conservation of PSC-CTR activity across metazoans. This conclusion could not have been determined from sequence alignments. We further find that plants that lack active PSC-CTRs instead possess a functionally analogous PcG protein, EMF1. Thus, our study suggests that a disordered domain with dispersed negative charges underlies PRC1 activity, and is conserved across metazoans and plants.