VIM methylcytosine-binding proteins and their role in epigenetic regulation

描述（由申请人提供）：提出了一项实验计划，以研究以前未表征的一类植物甲基胞嘧啶结合蛋白的遗传学、生物化学和细胞生物学。在筛选影响拟南芥胞嘧啶甲基化的自然变异时，发现了编码该家族一个成员的VIM 1（甲基化变异1）基因的突变。概述了四个具体目标，包括1）完成VIM 1、Vim旁系同源物和遗传修饰剂的遗传分析; 2）表征VIM 1、Vim旁系同源物和VIM 1样哺乳动物同源物的甲基胞嘧啶-DNA结合特异性; 3）调查VIMV在染色质修饰中的作用;和4）评估哺乳动物VIM 1样蛋白在胞嘧啶甲基化和表观遗传调控中的作用。拟议的实验计划将利用最重要的实验遗传系统之一中可用的工具和方法，该系统一直是我们对表观遗传调控的大部分知识的来源。基于拟南芥过去在哺乳动物表观遗传学中的应用，这一知识有望转化为哺乳动物系统。此外，结构和功能上与Vim蛋白相关的哺乳动物蛋白质也参与了致癌作用。该提案的几个子目标直接涉及这些蛋白质在哺乳动物细胞中的表观遗传调控中的作用。

DESCRIPTION (provided by applicant): An experimental plan is proposed to investigate the genetics, biochemistry, and cell biology of a previously uncharacterized class of plant methylcytosine binding proteins. Mutation in the VIM1 (Variant in Methylation 1) gene encoding one member of this family was uncovered in a screen for natural variation affecting cytosine methylation in Arabidopsis thaliana. Four specific aims are outlined, including 1) completion of genetic analysis of vim1, vim paralogs and genetic modifiers; 2) characterization of the methylcytosine-DNA binding specificty of VIM1, VIM paralogs, and VIM1-like mammalian homologs; 3) investigation of VIMVs role in chromatin modification; and 4) evaluation of the role of mammalian VIM1-like proteins in cytosine methyation and epigenetic regulation. The proposed experimental plan will exploit the tools and approaches available in one of the premier experimental genetic systems, which has been the source of much of our knowledge of epigenetic regulation. This knowledge promises to translate to mammalian systems, based on the strong record of past application of Arabidopsis work to mammalian epigenetics. In addition, mammalian proteins that are structurally and functionally related to VIM proteins have been implicated in carcinogenesis. Several subaims of the proposal directly address the role of these proteins in epigenetic regulation in mammalian cells.