Institute for Genomics and Systems Biology, Department of Human Genetics, and Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, USA.
PLoS Genet. 2010 Jan 15;6(1):e1000814. doi: 10.1371/journal.pgen.1000814.
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.
绝缘子是控制基因组调控元件相互作用的 DNA 序列，充当染色质边界。为了解决后生动物基因调控的复杂性，必须深入了解它们的位置和功能。我们通过 ChIP-chip 研究了 6 种绝缘子相关蛋白（dCTCF、CP190、BEAF-32、Su(Hw)、Mod(mdg4)和 GAF）的全基因组结合位点，获得了果蝇胚胎中绝缘子元件的第一张综合图谱。我们鉴定了超过 14000 个假定的绝缘子，包括所有经典定义的绝缘子。我们发现了两类主要的绝缘子，分别由 dCTCF/CP190/BEAF-32 和 Su(Hw)定义。绝缘子的分布分析表明，特定的绝缘子子类在顺式调控元件与其靶启动子之间被排除；区分差异表达、替代和发散的启动子；充当染色质边界；与物种间的染色体断点相关联；并嵌入活性染色质域内。总之，这些结果提供了一个图谱，划定了基因调控单元的边界，并为理解果蝇发育和进化过程中绝缘子的功能提供了一个框架。
