几种癌症相关的基因表达水平与表观遗传修饰关系研究

针对与肿瘤相关的DNA甲基化、组蛋白修饰和转录因子结合等表观遗传修饰数据增加，本项目拟在进一步完善和扩大与癌症相关的表观遗传修饰数据子库，分析癌组织(细胞)和正常组织(细胞)中差异表达基因和差异DNA甲基化和差异组蛋白修饰。研究DNA甲基化、组蛋白修饰、转录因子结合与基因差异表达的关系，探索这些表观遗传修饰在CpG岛、增强子和启动子等不同功能区域强度分布与相关基因表达水平的关系，特别是对癌基因和抑癌基因抑制的基因表达水平及其细胞特异性的影响。研究不同组蛋白修饰、转录因子结合和DNA甲基化的相互作用与基因表达水平的关系和细胞特异性，构建它们相互作用的调控网络。结合基因启动子区的序列信息、结构信息和组蛋白修饰、转录因子结合、DNA甲基化等表观修饰数据提出预测相关基因表达水平的理论模型和有效算法，探索表观遗传修饰与癌症发生的联系及其分子机理。

Based on the fast growth of the epigenetics modification data on the DNA methylation,histone modification and transcription factor binding signals, the some relative sub-dataset will be further completed and extended. The analysis of differential expression of genes，the differential DNA methylation and the differential histone modification between cancer tissue（cell）and normal tissue（cell）will be completed. The relations of the gene expression level with the DNA methylation, histone modification and transcription factor binding are investigated. The effect of the signal strength distribution of these epigenetic modification in CGI, enhancer and promoter etc functional regions on the expression level of gene will be analyzed, especially on the expression levels of oncogenes and tumor suppressor genes as well as their cell type-specific. The effect of the interactions of these different epigenetic modifications and transcription factor binding signals on the expression level of gene will be investigated. The regulatory network of the their interactions will be constructed. The novel model and algorithm for predicting gene expression level will be proposed by using the characteristic parameters of DNA methylation,histone modification and transcription factor binding signals combined with gene promoter sequence and structure information. The molecular mechanism and relation between epigenetic modifications and cancer will be explored.