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1.发明公开ECIST MICROARRAYS FOR DUAL SCREENING OF DNA HYPERMETHYLATION AND GENE SILENCING, AND FOR USE IN AN INTEGRATED SYSTEM FOR ASSESSING GENE EXPRESSION, DNA METHYLATION AND HISTONE ACETYLATION 审中-公开ECIST微阵列对于双筛选甲基化DNA和基因沉默和用在集成系统的评估基因表达，DNA甲基化和组蛋白乙酰化
公开(公告)号：EP1497447A2
公开(公告)日：2005-01-19
申请号：EP03721677.7
申请日：2003-04-14
发明人： HUANG, Tim, Hui-Ming , SHI, Huidong
CPC分类号： C12Q1/6809 , C12Q1/6827 , C12Q1/6837 , C12Q2565/501 , C12Q2525/143 , C12Q2525/149 , C12Q2521/331
摘要： Novel methods are herein provided for high-throughput, dual analysis of DNA methylation and gene expression, and triple analysis of DNA methylation, gene expression and gene-associated histone acetylation in cancer cells using arrayed expressed CpG island sequence tags (ECISTs). ECISTs correspond to genomic DNA fragments comprising GC-rich segments along with promoter and/or exon (e.g., first exon) portions of genes. The GC-rich segments are useful for screening hypermethylated CpG sites in cancer cells, while the corresponding promoter and exon-containing portions are useful for determining corresponding transcript levels and assessing histone acetylation. Also provided are high-throughput methods for either confirming methylation-dependent gene silencing, or identifying therapeutically effective demethylating agents, using the ECIST array panels to identify hypermethylated loci, and measure expression levels thereof after cellular exposure to demethylating agents. Further provided are high-throughput methods for distinguishing between direct (primary) demethylation-dependent gene up-regulation, and indirect (secondary) demethylation-dependent up-regulation within apparent epigenetic cascades.
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