The Plant KDM1C Histone Demethylase Repressor Complex

植物 KDM1C 组蛋白去甲基化酶阻遏复合物

• 批准号: 1118491
• 负责人: Vitaly Citovsky
• 金额: $ 80万
• 依托单位: SUNY at Stony Brook
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-11-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1118491&HistoricalAwards=false
• 关键词: Plant; KDM1C; Histone; Demethylase; Repressor

Intellectual Merit: Posttranslational histone modifications, e.g., methylation, acetylation, phosphorylation, and ubiquitination, play central roles in gene regulation in all eukaryotic organisms, determining the active or inactive state of the chromatin. Increasing evidence suggests that many such modifications do not act alone, but function in concert with each other, by a general mechanism known as histone modification crosstalk. One of the major, and perhaps the most interesting, pathways for histone modification crosstalk is the coordination of different histone-modifying enzymatic activities within the same regulator complex, which, in addition to histone-enzyme interactions, involves interactions between the enzymatic components of the regulator complex itself. As an experimental system, this project uses the plant KDM1C-SUVR5-OLD repressor complex. KDM1-based repressors play a key role in regulation of gene expression during such diverse and important processes as acquisition of neuron-specific traits in mammals and determination of flower timing in plants. Of all such repressors known to date, both in plants and animals, the plant KDM1C-SUVR5-OLD1 complex is unique because it contains a deubiquitinase activity, which has never before been observed associated with KDM1, and because one enzymatic activity (OLD1) depends on another (SUVR5). The project, therefore, aims to uncover aspects of chromatin-modifying repressor complexes that have not been observed in other model systems. This is achieved by pursuing two focused specific aims: (i) biochemical characterization of the KDM1C-SUVR5-OLD1 complex, and (ii) identification and initial characterization of a protein interaction network for activity of the KDM1C-SUVR5-OLD1 complex.Broader Impacts: The research is integrated into the teaching of science at the junior educational level, focusing on undergraduate students, who work on the projects and learn scientific thinking and modern experimentation. Specifically, the project anticipates involvement of three undergraduate students, who usually include underrepresented minorities recruited both from Stony Brook and via partnerships with Hunter College and Lehman College in New York City. In addition, the project aims to train high school teachers via Stony Brook?s Center for Science and Mathematics Education (CESAME), where the PI will teach a series of seminars and a summer workshop on epigenetics based on the concepts and results of this research. Finally, the project will train a postdoc to prepare this individual for an independent career in academia, biotech industry and/or Government agencies. Thus, this project promotes proactive outreach activities, which recruit students into the science pipeline, prepare beginning scientists for independent careers, and inform the public about science and technology.

智力优势：翻译后组蛋白修饰，例如，甲基化、乙酰化、磷酸化和泛素化在所有真核生物的基因调控中起着中心作用，决定了染色质的活性或非活性状态。越来越多的证据表明，许多这样的修饰并不单独起作用，而是通过称为组蛋白修饰串扰的一般机制相互协同起作用。组蛋白修饰串扰的主要途径之一，也许是最有趣的，是不同的组蛋白修饰酶活性在同一调节复合物内的协调，其中，除了组蛋白-酶相互作用，还涉及调节复合物本身的酶组分之间的相互作用。作为实验系统，本项目使用植物KDM 1C-SUVR 5-OLD阻遏物复合物。基于KDM 1的阻遏物在诸如哺乳动物神经元特异性性状的获得和植物开花时间的确定等多种重要过程中的基因表达调控中起关键作用。在迄今为止已知的植物和动物中的所有这些阻遏物中，植物KDM 1C-SUVR 5-OLD 1复合物是独特的，因为它含有去泛素化酶活性，这在以前从未观察到与KDM 1相关，并且因为一种酶活性（OLD 1）依赖于另一种酶活性（SUVR 5）。因此，该项目旨在揭示在其他模型系统中未观察到的染色质修饰阻遏物复合物的方面。这是通过追求两个集中的具体目标来实现的：（i）KDM 1C-SUVR 5-OLD 1复合物的生物化学表征，以及（ii）KDM 1C-SUVR 5-OLD 1复合物活性的蛋白质相互作用网络的鉴定和初步表征。这项研究被纳入初中教育水平的科学教学，重点是本科生，他们在项目中工作，学习科学思维和现代实验。具体而言，该项目预计将有三名本科生参与，他们通常包括从斯托尼布鲁克以及通过与纽约市的亨特学院和雷曼学院的伙伴关系招募的代表性不足的少数群体。此外，该项目旨在通过斯托尼布鲁克培训高中教师？该中心的科学和数学教育（CEESTO），在那里PI将讲授一系列研讨会和暑期讲习班表观遗传学的基础上的概念和这项研究的结果。最后，该项目将培养一名博士后，为这个人在学术界，生物技术行业和/或政府机构的独立职业生涯做好准备。因此，该项目促进积极主动的外联活动，招募学生进入科学管道，为独立职业的初出茅庐的科学家做好准备，并向公众宣传科学和技术。