STRUCTURAL STUDIES OF EPIGENETIC REGULATORS

表观遗传调控因子的结构研究

• 批准号: 8363362
• 负责人: Karim Jean Armache
• 金额: $ 0.25万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363362
• 关键词: Area; Binding; Biochemical; Cell Differentiation process; Cells; Chromatin; Chromatin Structure; Complex; Crystallography; Data; Development; Drosophila genus; Epigenetic Process; Evolution; Funding; Gene Silencing; Gene Targeting; Genetic; Grant; Heterochromatin; Light; Maintenance; Malignant Neoplasms; National Center for Research Resources; Nucleosomes; PRC1 Protein; Physical condensation; Polycomb; Principal Investigator; Proteins; Repression; Research; Research Infrastructure; Resources; Role; Source; Structure; Synchrotrons; System; United States National Institutes of Health; base; cell growth; cost; design; gene repression; insight; novel; research study; telomere

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In the cell, repressed chromatin domains are thought to be regulated by factors that bind specifically to these loci. One such protein, HP1, is associated with pericentric heterochromatin and telomeres in Drosophila. An example of a complex is the Polycomb group complex, PRC1. Polycomb proteins are involved in the maintenance of repression of target genes during development.The structures of epigenetic regulators in complex with nucleosome arrays will provide us with mechanistic insights into chromatin condensation. These data should give novel insights into transcription repression mechanisms, the specific features of the chromatin structures that contribute to this repression and the evolution of repressive machineries. The results will help interpretation of genetic and biochemical data available on the PRC1 and HP1 systems, and will enable the design of new functional experiments. Given the important roles of these proteins in regulating cell growth and differentiation, and in cancer development, structural data of PRC1 and HP1 will be beneficial also for this area of research. An understanding of the mechanisms by which the PcG proteins and HP1 perform their role will be central to the development of novel therapies based on epigenetic gene silencing.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 在细胞中，抑制的染色质结构域被认为受到与这些位点特异性结合的因子的调节。其中一种蛋白质 HP1 与果蝇的中心周异染色质和端粒相关。配合物的一个例子是 Polycomb 群配合物 PRC1。多梳蛋白参与发育过程中靶基因抑制的维持。与核小体阵列复合的表观遗传调节因子的结构将为我们提供染色质浓缩的机制见解。这些数据应该为转录抑制机制、有助于这种抑制的染色质结构的具体特征以及抑制机制的进化提供新的见解。结果将有助于解释 PRC1 和 HP1 系统上可用的遗传和生化数据，并将有助于设计新的功能实验。鉴于这些蛋白质在调节细胞生长和分化以及癌症发展中的重要作用，PRC1 和 HP1 的结构数据也将有利于该领域的研究。了解 PcG 蛋白和 HP1 发挥作用的机制对于开发基于表观遗传基因沉默的新型疗法至关重要。