STRUCTURAL STUDIES OF EPIGENETIC REGULATORS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在细胞中，被抑制的染色质结构域被认为是由与这些基因位点特异结合的因素调节的。其中一种蛋白质HP1与果蝇的中心周围异染色质和端粒有关。复合体的一个例子是多梳基团复合体，Prc1。多梳蛋白在发育过程中参与维持靶基因的抑制，与核小体阵列形成复合体的表观遗传调控结构将为我们提供对染色质缩合的机械性见解。这些数据应该会为转录抑制机制、导致这种抑制的染色质结构的特定特征以及抑制机制的进化提供新的见解。这些结果将有助于解释PRC1和HP1系统上可用的遗传和生化数据，并将使新的功能实验的设计成为可能。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的结构数据也将有助于这一领域的研究。了解PcG蛋白和HP1发挥作用的机制将是开发基于表观遗传基因沉默的新疗法的核心。

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.