Triple analysis of the cancer epigenome: an integrated microarray system for assessing gene expression, DNA methylation, and histone acetylation.
Triple analysis of the cancer epigenome: an integrated microarray system for assessing gene expression, DNA methylation, and histone acetylation.
复制标题
DOI：
--
复制
发表时间：
2003-05
期刊：
影响因子：
11.2
通讯作者：
Huidong Shi;Susan H. Wei;Yu‐Wei Leu;F. Rahmatpanah;Joseph C. Liu;P. Yan;K. Nephew;T. Huang
中科院分区：
文献类型：
--
作者：
Huidong Shi;Susan H. Wei;Yu‐Wei Leu;F. Rahmatpanah;Joseph C. Liu;P. Yan;K. Nephew;T. Huang
我们开发了一种新的微阵列系统，以评估基因表达，DNA甲基化和组蛋白乙酰化平行，并剖析癌症的表观遗传变化的复杂层次。使用由位于5 '端区域（包括第一外显子）的1507个短CpG岛标签组成的整合微阵列面板来评估表观遗传治疗对人上皮性卵巢癌细胞系的影响。单独使用甲基化（5-氮杂-2 '-脱氧胞苷）或去乙酰化（阿司他汀A）抑制剂治疗导致1.9%或1.1%的分析基因上调;然而，联合治疗导致更多基因的协同再激活（10.4%; P < 0.001，与单独使用任一种治疗相比）。根据对处理的初级或次级反应，将基因鉴定为甲基化依赖性或非依赖性。5-氮杂-2 '-脱氧胞苷加抑制素A对甲基化依赖性基因的协同再激活揭示了甲基化启动子和去乙酰化组蛋白之间的功能性相互作用。一些甲基化非依赖性基因的表达增加与增强的组蛋白乙酰化相关，但使用该技术鉴定的大多数基因的上调是由于表观遗传级联的下游事件。我们证明了使用三重微阵列系统在分析癌症基因组中转录因子和启动子靶点之间的动态关系的原理。
We developed a novel microarray system to assess gene expression, DNA methylation, and histone acetylation in parallel, and to dissect the complex hierarchy of epigenetic changes in cancer. An integrated microarray panel consisting of 1507 short CpG island tags located at the 5'-end regions (including the first exons) was used to assess effects of epigenetic treatments on a human epithelial ovarian cancer cell line. Treatment with methylation (5-aza-2'-deoxycytidine) or deacetylation (trichostatin A) inhibitors alone resulted in up-regulation of 1.9 or 1.1% of the genes analyzed; however, the combined treatment resulted in synergistic reactivation of more genes (10.4%; P < 0.001 versus either treatment alone). On the basis of either primary or secondary responses to the treatments, genes were identified as methylation-dependent or -independent. Synergistic reactivation of the methylation-dependent genes by 5-aza-2'-deoxycytidine plus trichostatin A revealed a functional interaction between methylated promoters and deacetylated histones. Increased expression of some methylation-independent genes was associated with enhanced histone acetylation, but up-regulation of most of the genes identified using this technology was because of events downstream of the epigenetic cascade. We demonstrate proof of principle for using the triple microarray system in analyzing the dynamic relationship between transcription factors and promoter targets in cancer genomes.