ESTABLISHING SUB-NUCLEAR DOMAINS OF COORDINATE GENE REGULATION

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 协调基因调控是从生殖系到免疫系统的所有细胞所必需的基本生物学过程。在自闭症、克罗恩病和唐氏综合症等多种疾病中，调节被破坏。X染色体剂量补偿是研究这一过程的最佳模型之一，因为成千上万的基因被共同调节。与哺乳动物一样，果蝇的单个雄性X染色体上的大量不同基因的转录水平沿着增加，相对于每个雌性X染色体和所有其他染色体，增加了两倍。果蝇雄性特异性致死（MSL）复合物是剂量补偿的核心。长期以来，人们提出MSL复合物首先识别男性X染色体上的高亲和力位点，然后沿其长度沿着扩散。然而，由于在获得足够的生物化学材料方面的限制，没有时间数据支持这一假设。因此，我们将开发一种创新的细胞诱导系统，以产生足够的材料来进行染色质免疫沉淀，然后在许多时间点进行NextGen测序（ChIPseq）。我们希望这个试点项目将产生第一个系统来定义亚核结构域如何在物种间实时形成，并为NIH R 01提供坚实的基础。

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. Coordinate gene regulation is a fundamental biological process essential to all cells from the germ line to the immune system. Regulation is disrupted in disorders as diverse as autism, Crohn's disease, and Down's syndrome. X-chromosome dosage compensation is one of the best models for studying this process because thousands of genes are co-regulated. Drosophila, like mammals, increase the transcript levels from a large number of diverse genes along the single male X-chromosome precisely two-fold relative to each female X-chromosome and all other chromosomes. The Drosophila Male Specific Lethal (MSL) complex is central to dosage compensation. It has long been proposed that MSL complex first identifies high affinity sites on the male X-chromosome and then spreads along its length. However, there is no temporal data to support this hypothesis due to limitations in obtaining sufficient material for biochemistry. Therefore, we will develop an innovative cell induction system to generate sufficient material to perform chromatin immunoprecipitation followed by NextGen sequencing (ChIPseq) at many time points. We expect that this pilot project will generate the first system to define how sub-nuclear domains are formed in real-time across species and provide a strong foundation for an NIH R01.