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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 在细胞中，抑制染色质结构域被认为是由特异性结合这些基因座的因素调节的。一种这样的蛋白质HP1与果蝇中的上十大异染色质和端粒有关。复合物的一个例子是Polycomb组复合物PRC1。多肉蛋白参与了发育过程中靶基因抑制的维持。与核小体阵列复杂的表观遗传调节剂的结构将为我们提供对染色质缩合的机械洞察力。这些数据应提供对转录抑制机制的新见解，这是染色质结构的特定特征，这些特征有助于这种抑制作用和压抑机械的演变。结果将有助于解释PRC1和HP1系统上可用的遗传和生化数据，并可以设计新的功能实验。鉴于这些蛋白质在调节细胞生长和分化以及在癌症发展中的重要作用，PRC1和HP1的结构数据也将对这一研究领域有益。对PCG蛋白和HP1发挥作用的机制的理解对于基于表观遗传基因沉默的新疗法的发展至关重要。