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VIM1（甲基化变异1）基因突变。具体目标包括：1)完成vim1、vim类似物和基因修饰物的遗传分析；2)鉴定了VIM1、VIM1类似物和VIM1样哺乳动物同源物的甲基胞嘧啶- dna结合特异性；3) vimv在染色质修饰中的作用研究；4)评估哺乳动物vim1样蛋白在胞嘧啶甲基化和表观遗传调控中的作用。提出的实验计划将利用在一个主要的实验遗传系统中可用的工具和方法，这是我们对表观遗传调控的许多知识的来源。基于以往拟南芥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，在结构和功能上与VIM蛋白相关的哺乳动物蛋白与癌变有关。该提案的几个子目标直接解决了这些蛋白质在哺乳动物细胞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.