Heisler Lawrence E, Torti Dax, Boutros Paul C, Watson John, Chan Charles, Winegarden Neil, Takahashi Mark, Yau Patrick, Huang Tim H-M, Farnham Peggy J, Jurisica Igor, Woodgett James R, Bremner Rod, Penn Linda Z, Der Sandy D
Department of Laboratory Medicine and Pathobiology, Program in Proteomics and Bioinformatics, University of Toronto Toronto, ON M5S 1A8, Canada.
Nucleic Acids Res. 2005 May 23;33(9):2952-61. doi: 10.1093/nar/gki582. Print 2005.
An effective tool for the global analysis of both DNA methylation status and protein-chromatin interactions is a microarray constructed with sequences containing regulatory elements. One type of array suited for this purpose takes advantage of the strong association between CpG Islands (CGIs) and gene regulatory regions. We have obtained 20,736 clones from a CGI Library and used these to construct CGI arrays. The utility of this library requires proper annotation and assessment of the clones, including CpG content, genomic origin and proximity to neighboring genes. Alignment of clone sequences to the human genome (UCSC hg17) identified 9595 distinct genomic loci; 64% were defined by a single clone while the remaining 36% were represented by multiple, redundant clones. Approximately 68% of the loci were located near a transcription start site. The distribution of these loci covered all 23 chromosomes, with 63% overlapping a bioinformatically identified CGI. The high representation of genomic CGI in this rich collection of clones supports the utilization of microarrays produced with this library for the study of global epigenetic mechanisms and protein-chromatin interactions. A browsable database is available on-line to facilitate exploration of the CGIs in this library and their association with annotated genes or promoter elements.
一种用于对DNA甲基化状态和蛋白质-染色质相互作用进行全局分析的有效工具是用含有调控元件的序列构建的微阵列。一种适用于此目的的阵列类型利用了CpG岛(CGI)与基因调控区域之间的强关联。我们从一个CGI文库中获得了20,736个克隆,并使用这些克隆构建了CGI阵列。该文库的实用性需要对克隆进行适当的注释和评估,包括CpG含量、基因组来源以及与相邻基因的距离。将克隆序列与人基因组(UCSC hg17)进行比对,确定了9595个不同的基因组位点;64%由单个克隆定义,其余36%由多个冗余克隆代表。大约68%的位点位于转录起始位点附近。这些位点的分布覆盖了所有23条染色体,其中63%与通过生物信息学鉴定的CGI重叠。在这个丰富的克隆集合中基因组CGI的高比例代表支持利用用该文库产生的微阵列来研究全局表观遗传机制和蛋白质-染色质相互作用。一个可浏览的数据库在线可用,以促进对该文库中CGI及其与注释基因或启动子元件关联的探索。