人类心脏发育候选基因ZNF569的研究

发布时间：2018-01-05 06:25

本文关键词：人类心脏发育候选基因ZNF569的研究　出处：《湖南师范大学》2005年硕士论文　论文类型：学位论文

【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
[Abstract]:Cardiovascular disease has become one of the two greatest threats to human health. In the study of cardiovascular diseases, it has been found that the disorder of the expression of some genes in time and space can lead to congenital heart disease. The study of some people with high incidence of cardiovascular diseases also proved that some acquired heart disease is related to genetic factors. Our lab carried out large-scale screening to clone human heart development related genes to understand. The mechanism of heart development. Exploring the molecular regulation mechanism of heart development has laid a solid foundation. ZNF569 is a new human gene. ZNF569, which the author found in the process of screening candidate genes for human heart development using bioinformatics. The length of cDNA was 4071 bases. ORF is 2061 bases in length and encodes a 686 amino acid residues. The protein contains a KRAB domain and 18 zinc finger domains in mice and rats. Its homologous proteins have been found in many species including Drosophila, and there is a high similarity between them. Northern results showed that ZNF569 was highly expressed in adult liver, heart and placenta. The expression was weak in pancreas and skeletal muscle, but also in fetal heart, skeletal muscle and liver. The transcriptional activity analysis showed that overexpression of ZNF569 protein in COS-7 cells could cause two downstream transcription factors AP-1 and SR of MAPK signaling pathway. The subcellular localization analysis of ZNF569 in nuclear and cytoplasm further demonstrated its role as a transcription factor. Segmented report for ZNF569. Assays analysis showed that. ZNF569 may play a role in inhibiting transcription through KRAB frame and C2H2 zinc finger domain. ZNF569 may participate in the regulation of cell life through MAPK signaling pathway. The author also describes a Rho family GTPases exchange factor, hGEFT.
【学位授予单位】：湖南师范大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R346

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