组蛋白修饰和DNA甲基化对球虫发育阶段转化和早熟发育的调控机理研究

项目名称： 组蛋白修饰和DNA甲基化对球虫发育阶段转化和早熟发育的调控机理研究

项目编号： No.31272554

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 农业科学

项目作者： 蔡建平

作者单位： 中国农业科学院兰州兽医研究所

项目金额： 83万元

中文摘要： 艾美耳球虫具有生活史过程复杂并具有早熟性，生活史各阶段的转化过程中存在形态学、抗原性和毒力因子的明显差异，早熟系毒力减弱但保留免疫原性。探讨阶段转化和早熟形成的调控机理，是深入理解球虫与宿主相互作用及免疫激发机理、药靶筛选和新药开发的理论基础。基因组数据分析表明，球虫相对缺乏与基因表达调控相关的DNA结合的顺式转录因子，而富有组蛋白和DNA甲基化修饰的相关蛋白编码基因，提示表观遗传可能是其主要的基因表达调控方式。本研究拟采用ChIP-Seq和BS-Seq技术对柔嫩艾美耳球虫及其早熟系不同生活史阶段虫体进行基因组水平的表观遗传组测序，以揭示二者在基因组水平上的蛋白质结合位点(转录因子结合位点)和DNA甲基化率与甲基化模式，挖掘与球虫发育阶段转化相关的特定基因，解析组蛋白修饰的染色质重塑和DNA甲基化对球虫生活史中阶段转化和分化及早熟发育的调控机理。研究结果对球虫病防治重要的理论指导意义。

中文关键词： 柔嫩艾美耳球虫；DNA甲基化；组蛋白去乙酰化酶；翻译后修饰；DNA甲基转移酶

英文摘要： Eimeria spp., the pathogen of the animal coccidiosis, is an absolute intracellular parasite belong to Apicomplexa phylum. These parasites are highly host-specific, present a monoxenous life cycle in which there are complicated developmental stage coversions, and can be selected as a vaccine candidate by their precocious phenotype. In different developmental stage and precocious line, their morphologies, virulence, and gene expressions will be changed through the gene regulatory machinery. Profiling the regulatory mechanisms for this stage conversion is an interesting and important for deeply understanding the parasite-host interaction, immunoresponses triggering, and finding new validate drug targets. The global genome data analysis reveals that their developmental stage conversion and gene expression could be regulated and controlled by mainly relying on the epigenetic mechanisms like histome modification and DNA methylation, since their DNA-binding cis-transcripting factors coding genes are relatively low. However, relatively rich histone modifying proteins and DNA methylase coding sequences are harbored in their genome data. This gene distribution bias could implicate a novel epigenetic regulatory mechanism is in charge of their gene expression regulation for their stage conversion, differentiation and prec

英文关键词： Eimeria tenella；DNA methylation；Histone deacetylase；post-translational modification；DNA methyltransferase