A comprehensive map of insulator elements for the Drosophila genome.
A comprehensive map of insulator elements for the Drosophila genome.
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DOI：
10.1371/journal.pgen.1000814
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发表时间：
2010-01-15
期刊：
影响因子：
4.5
通讯作者：
White KP
中科院分区：
文献类型：
--
作者：
Nègre N;Brown CD;Shah PK;Kheradpour P;Morrison CA;Henikoff JG;Feng X;Ahmad K;Russell S;White RA;Stein L;Henikoff S;Kellis M;White KP
绝缘子是控制基因组调控元件之间相互作用并充当染色质边界的DNA序列。彻底了解他们的位置和功能是必要的，以解决后生动物基因调控的复杂性。我们利用ChIP芯片研究了6种绝缘子相关蛋白dCTCF、CP 190、BEAF-32、Su（Hw）、Mod（mdg 4）和GAF的全基因组结合位点，首次获得了果蝇胚胎绝缘子元件的完整图谱。我们确定了超过14，000个假定的绝缘体，包括所有经典定义的绝缘体。我们发现两个主要类别的绝缘子定义的dCTCF/CP 190/BEAF-32和苏（Hw），分别。绝缘子的分布分析表明，特定的亚类绝缘子元件被排除在顺式调控元件和它们的目标启动子之间;划分差异表达，替代和发散启动子;作为染色质边界;与物种之间的染色体断裂点;并嵌入在活性染色质结构域。总之，这些结果提供了一个地图划定基因调控单位的边界和框架，了解绝缘子功能的发展和进化过程中的果蝇。基因表达的时空特异性受调控蛋白、顺式调控元件、染色质修饰和基因之间的相互作用控制。这些相互作用可以在很远的距离上发生，并且对其控制的机制知之甚少。绝缘子是DNA序列，既可以阻止调控元件和基因之间的相互作用，也可以阻止修饰的染色质区域的扩散。迄今为止，在发育中的果蝇胚胎中发现的绝缘体相对较少。我们在此展示了6种胰岛素相关蛋白的14，000多个结合位点的全基因组鉴定。我们证明了两大类绝缘体的存在。这两类绝缘子在特定染色质修饰的边界处富集。然而，只有BEAF-32，CP 190和dCTCF结合的绝缘子在开放的染色质区域富集或划分基因边界，在差异表达的启动子之间具有特定的富集。此外，这类绝缘子富集在染色体重排的12种测序果蝇之间的点，这表明绝缘子定义的监管边界是进化保守的。
Insulators are DNA sequences that control the interactions among genomic regulatory elements and act as chromatin boundaries. A thorough understanding of their location and function is necessary to address the complexities of metazoan gene regulation. We studied by ChIP–chip the genome-wide binding sites of 6 insulator-associated proteins—dCTCF, CP190, BEAF-32, Su(Hw), Mod(mdg4), and GAF—to obtain the first comprehensive map of insulator elements in Drosophila embryos. We identify over 14,000 putative insulators, including all classically defined insulators. We find two major classes of insulators defined by dCTCF/CP190/BEAF-32 and Su(Hw), respectively. Distributional analyses of insulators revealed that particular sub-classes of insulator elements are excluded between cis-regulatory elements and their target promoters; divide differentially expressed, alternative, and divergent promoters; act as chromatin boundaries; are associated with chromosomal breakpoints among species; and are embedded within active chromatin domains. Together, these results provide a map demarcating the boundaries of gene regulatory units and a framework for understanding insulator function during the development and evolution of Drosophila. The spatiotemporal specificity of gene expression is controlled by interactions among regulatory proteins, cis-regulatory elements, chromatin modifications, and genes. These interactions can occur over large distances, and the mechanisms by which they are controlled are poorly understood. Insulators are DNA sequences that can both block the interaction between regulatory elements and genes, as well as block the spread of regions of modified chromatin. To date, relatively few insulators have been identified in developing Drosophila embryos. We here present the genome wide identification of over 14,000 binding sites for 6 insulator-associated proteins. We demonstrate the existence of two broad classes of insulators. Insulators of both classes are enriched at the boundaries of a particular chromatin modification. However, only insulators bound by BEAF-32, CP190, and dCTCF are enriched in regions of open chromatin or demarcate gene boundaries, with a particular enrichment between differentially expressed promoters. Furthermore, insulators of this class are enriched at points of chromosomal rearrangement among the 12 species of sequenced Drosophila, suggesting that insulator defined regulatory boundaries are evolutionarily conserved.
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