Three subclasses of a Drosophila insulator show distinct and cell type-specific genomic distributions
Three subclasses of a Drosophila insulator show distinct and cell type-specific genomic distributions
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DOI：
10.1101/gad.1798209
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发表时间：
2009-06-01
影响因子：
10.5
通讯作者：
Corces, Victor G.
中科院分区：
文献类型：
--
作者：
Bushey, Ashley M.;Ramos, Edward;Corces, Victor G.
绝缘子是蛋白质结合的DNA元件，被认为在染色质组织中发挥作用，并通过介导染色体内和染色体间相互作用调节基因表达。毛翼抑制因子[Su(Hw)]和果蝇CTCF （dCTCF）绝缘子存在于果蝇基因组的不同位点，并通过募集额外的蛋白中心体蛋白190 （CP190）发挥作用。我们利用全基因组切片阵列进行了染色质免疫沉淀（ChIP）和芯片分析（ChIP- ChIP）实验，比较了两种不同细胞系中Su（Hw）、dCTCF、边界元件相关因子（BEAF）和CP190在DNA上的定位，发现BEAF是含CP190绝缘体的第三个亚类。dna结合蛋白Su（Hw）、dCTCF和BEAF在基因的位置和表达水平方面表现出独特的分布模式，表明这三种绝缘子亚类在基因组组织中的作用不同。值得注意的是，所有三种dna结合蛋白以及CP190的细胞系特异性定位位点表明，绝缘子可以在多个水平上调节以影响基因表达。这些发现提示了一个模型，其中绝缘子亚类可能具有不同的功能，它们以细胞类型特异性的方式共同组织基因组，从而导致基因表达的差异调节。
Insulators are protein-bound DNA elements that are thought to play a role in chromatin organization and the regulation of gene expression by mediating intra-and interchromosomal interactions. Suppressor of Hair-wing [Su(Hw)] and Drosophila CTCF (dCTCF) insulators are found at distinct loci throughout the Drosophila melanogaster genome and function by recruiting an additional protein, Centrosomal Protein 190 (CP190). We performed chromatin immunoprecipitation (ChIP) and microarray analysis (ChIP-chip) experiments with whole-genome tiling arrays to compare Su(Hw), dCTCF, boundary element-associated factor (BEAF), and CP190 localization on DNA in two different cell lines and found evidence that BEAF is a third subclass of CP190-containing insulators. The DNA-binding proteins Su(Hw), dCTCF, and BEAF show unique distribution patterns with respect to the location and expression level of genes, suggesting diverse roles for these three subclasses of insulators in genome organization. Notably, cell line-specific localization sites for all three DNA-binding proteins as well as CP190 indicate multiple levels at which insulators can be regulated to affect gene expression. These findings suggest a model in which insulator subclasses may have distinct functions that together organize the genome in a cell type-specific manner, resulting in differential regulation of gene expression.