【作者】 黄欣琼；

【导师】 吴秀山； 袁婺洲；

【作者基本信息】 湖南师范大学 ， 分子发育遗传学， 2005， 硕士

【摘要】 心血管系统疾病已经成为威胁人类健康的最大的两个敌人之一。在心血管系统疾病的研究中已发现,某些基因在时空上的表达紊乱可导致先天性心脏病,而对部分心血管系统病症高发人群的研究也证明部分后天形成的心脏病与遗传因素有关。我们研究室进行的大规模筛选克隆人类心脏发育的相关基因工作为理解心脏发育的机理、探索心脏发育中的分子调控机制打下了坚实的基础。 ZNF569就是本文作者在利用生物信息学方法筛选人类心脏发育候选基因的过程中发现的一个人类新基因。ZNF569 cDNA全长4071个碱基,ORF全长2061个碱基,编码一个长686个氨基酸残基的蛋白质。该蛋白包含一个KRAB结构域和18个锌指结构域,在包括小鼠、大鼠、果蝇在内的多个物种中均发现了它的同源蛋白,并且它们之间具有极高的相似度,说明此蛋白所在的亚家族可能具有相当重要的功能。Northern结果显示ZNF569在成人的肝、心脏和胎盘中有高表达,在胰腺和骨骼肌中表达较弱,在胚胎心脏、骨骼肌和肝也有表达,提示该基因可能与心脏发育有关。转录活性分析表明在COS-7细胞中过表达ZNF569蛋白可以使MAPK信号途径的两个下游转录因子AP-1和SRE的转录抑制活性显著下降。ZNF569在核质内的亚细胞定位分析进一步证明了其作为转录因子的作用。对ZNF569的分段report assays分析表明,ZNF569可能通过KRAB框和C2H2锌指结构域行使其抑制转录的作用。综合目前的研究结果来看,ZNF569可以通过MAPK信号途径参与了对细胞生命活动的调控过程。 本文作者还对一个Rho family GTPases交换因子hGEFT进行了更多还原

【Abstract】 Cardiovascular diseases have become one of the two kinds of most serious diseases that threaten human beings. It is a critical prerequisite to understand the normal progress of cardiovascular development and the mechanisms underlying the causes of this kind of diseases, so it is possible to cure the disease. As it known, mistakes in spatiotemporal expression of critical genes result in congenital cardiovascular diseases. Furthermore, studies on high risk population of cardiovascular disease have also suggested the relationship between noncongenital cardiovascular diseases and genetic factors. In order to promote our understanding for cardiovascular development and to discover the molecular regulatory mechanisms during this progress, our laboratory performed a large scale scanning project to search and clone cardiac developmental candidate genes.In the present study, we report the identification and characterization of a novel KRAB-containing zinc-finger protein, ZNF569, from a human embryonic heart cDNA library. ZNF569 encodes a putative protein of 686 amino acids. The protein is conserved across different species during evolution. Northern blot analysis indicates that ZNF569 is expressed in heart, liver, placenta, muscles, and pancreas and in a very embryonic development-specific stage of human tissues, including heart, pancreas,更多还原