VIM methylcytosine-binding proteins and their role in epigenetic regulation

VIM 甲基胞嘧啶结合蛋白及其在表观遗传调控中的作用

• 批准号: 7781848
• 负责人: ERIC JEAN RICHARDS
• 金额: $ 22.01万
• 依托单位: BOYCE THOMPSON INST FOR PLANT RESEARCH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7781848
• 关键词: Address; Affect; Arabidopsis; Binding; Binding Proteins; Biochemistry; Cellular biology; Chromatin; Class; Cytosine; DNA; DNA Binding; Defect; Epigenetic Process; Evaluation; Experimental Genetics; Family; Family member; Genes; Genetic; Histones; Homologous Gene; Investigation; Knowledge; Maintenance; Mammalian Cell; Methylation; Modification; Mouse-ear Cress; Mutation; Plants; Protein Binding; Proteins; Regulation; Role; Source; System; Translating; Variant; Work; base; carcinogenesis; genetic analysis; loss of function mutation; paralogous gene; tool; ubiquitin ligase

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.

描述（由申请人提供）：提出了一项实验计划来研究先前未表征的植物甲基胞嘧啶结合蛋白类别的遗传学、生物化学和细胞生物学。在对影响拟南芥胞嘧啶甲基化的自然变异的筛选中，发现了编码该家族一名成员的 VIM1（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vim1、vim旁系同源物和遗传修饰剂的遗传分析； 2) VIM1、VIM旁系同源物和VIM1样哺乳动物同源物的甲基胞嘧啶-DNA结合特异性的表征； 3) 研究VIMVs在染色质修饰中的作用； 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。拟议的实验计划将利用主要实验遗传系统之一中可用的工具和方法，该系统是我们许多表观遗传调控知识的来源。基于过去拟南芥工作在哺乳动物表观遗传学中的应用的良好记录，这些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也与癌症发生有关。该提案的几个子目标直接解决这些蛋白质在哺乳动物细胞表观遗传调控中的作用。