Nature and function of insulator protein binding sites in the Drosophila genome.
Nature and function of insulator protein binding sites in the Drosophila genome.
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DOI：
10.1101/gr.138156.112
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发表时间：
2012-11
期刊：
影响因子：
7
通讯作者：
Pirrotta V
中科院分区：
文献类型：
--
作者：
Schwartz YB;Linder-Basso D;Kharchenko PV;Tolstorukov MY;Kim M;Li HB;Gorchakov AA;Minoda A;Shanower G;Alekseyenko AA;Riddle NC;Jung YL;Gu T;Plachetka A;Elgin SC;Kuroda MI;Park PJ;Savitsky M;Karpen GH;Pirrotta V
染色质绝缘体元件和相关蛋白被认为将真核生物基因组划分为独立调控的结构域。在这里，我们通过对果蝇染色质绝缘子蛋白结合的全基因组定量分析来验证这一假设。我们发现了不同类型的绝缘子蛋白与不同位点的独特组合结合，并发现了一种新的绝缘子元件，它与CP190结合，而不是与任何其他已知的绝缘子蛋白结合。不同类型结合位点的功能表征表明，在标准的增强剂阻断试验中，只有一小部分作为健壮的绝缘体。我们发现绝缘子限制了H3K27me3标记的传播，但仅在少数Polycomb靶区，并且仅在已经转录失活的邻近基因中阻止抑制性组蛋白甲基化。RNAi敲低培养细胞中的绝缘子蛋白不会导致基因组表达的重大改变。综上所述，这些观察结果反驳了基因组被特殊边界元素分割的概念，并表明绝缘子是为选定基因的特定调节而保留的。
Chromatin insulator elements and associated proteins have been proposed to partition eukaryotic genomes into sets of independently regulated domains. Here we test this hypothesis by quantitative genome-wide analysis of insulator protein binding to Drosophila chromatin. We find distinct combinatorial binding of insulator proteins to different classes of sites and uncover a novel type of insulator element that binds CP190 but not any other known insulator proteins. Functional characterization of different classes of binding sites indicates that only a small fraction act as robust insulators in standard enhancer-blocking assays. We show that insulators restrict the spreading of the H3K27me3 mark but only at a small number of Polycomb target regions and only to prevent repressive histone methylation within adjacent genes that are already transcriptionally inactive. RNAi knockdown of insulator proteins in cultured cells does not lead to major alterations in genome expression. Taken together, these observations argue against the concept of a genome partitioned by specialized boundary elements and suggest that insulators are reserved for specific regulation of selected genes.
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