动物组蛋白H3K4三甲基化转移酶MLL3的生物信息学分析(英文)

[目的]对动物组蛋白H3K4三甲基化转移酶MLL3进行生物信息学分析,从而探寻其相对保守的进化过程以揭示组蛋白H3K4三甲基化转移酶MLL3在在人类癌症的中的作用。[方法]利用生物信息学的方法,对小鼠MLL3的基因结构、氨基酸序列、系统进化树、染色体定位和共线性等问题进行分析。[结果]编码合成的小鼠MLL3蛋白质一级结构包括7个锌指结构域、1个HMG-box(高迁移率族蛋白)、1个FYRN(N-末端富含苯丙氨酸或酪氨酸区域)、1个FYRC(C-末端富含苯丙氨酸或酪氨酸区域)、1个SET域和1个postSET域;从序列对比和同源性上发现,该研究中的19种动物都基本上具有这些结构,说明这些结构在进化上是相对保守的,其中SET域具有高度的保守性,是维持组蛋白甲基化酶活性所必须的;从系统发生上看,19种动物在进化树上的位置与其分类地位相一致;在共线性分析中,虽然小鼠和人的MLL3基因位于不同的染色体上,但其上游和下游具有相同的基因,说明小鼠和人的MLL3基因具有共线性。[结论]不仅揭示了MLL3的核苷酸序列及其氨基酸序列的一级结构,为以后研究其高级结构和蛋白质的功能奠定了基础;同时也为后期进行小鼠MLL3基因的引物设计、启动子分析、基因的克隆、定位和表达的调控模式研究奠定了基础。

Bioinformatics Analysis on Histone H3-lys-4 Methyltransferase MLL3

[Objective] This study aimed to conduct bioinformatics analysis of histone H3-lys-4(H3K4) methyltransferase MLL3 in animals,thus exploring its relatively conservative evolution to reveal the role of histon H3K4 trimethyltransferase MLL3 in human cancers.[Method] By using bioinformatics method,gene structure,amino acid sequences,phylogenetic tree,chromosomal localization and synteny of mouse MLL3 were analyzed.[Result] Primary structure of the encoded mouse MLL3 protein contained seven zinc finger domains,an HMG-box(High mobility group-box protein),a FYRN(F/Y-rich N-terminus) domain,a FYRC(F/Yrich C-terminus) domain,a SET domain and a postSET domain.Results of sequence comparison and homology showed that 19 animal species in this study all had these structures basically,which indicated that these structures were relatively conserved in the evolution;specifically,the SET domain was highly conserved and was necessary to maintain the activity of histone methyltransferases.Results of phylogenetic analysis showed that the locations of the 19 animal species in evolutionary tree were consistent with the taxonomic status.Results of synteny analysis showed that there were the same gene in the upstream and downstream of the mouse and human MLL3 gene which were located on different chromosomes,indicating that the mouse and human MLL3 gene had collinearity.[Conclusion] This study had revealed the primary structure of MLL3 nucleotide sequence and amino acid sequence,which had not only laid the foundation for the future research of high-level structure and function of MLL3 protein but also provided the basis for the follow-up study of primer design,promoter analysis,gene cloning and regulation patterns of localization and expression of mouse MLL3 gene.