ESTABLISHING SUB-NUCLEAR DOMAINS OF COORDINATE GENE REGULATION

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。 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。自闭症、克罗恩病和唐氏综合症等各种疾病的调节都被打乱了。X染色体剂量补偿是研究这一过程的最佳模型之一，因为数千个基因是共同调节的。果蝇和哺乳动物一样，在单个雄性X染色体上，大量不同基因的转录水平比每个雌性X染色体和所有其他染色体精确地增加了两倍。果蝇雄性特异性致死(MSL)复合体是剂量补偿的中心。长期以来，人们一直认为MSL复合体首先识别男性X染色体上的高亲和力部位，然后沿其长度传播。然而，由于在获得足够的生物化学材料方面的限制，没有时间数据来支持这一假设。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，然后在多个时间点进行下一代测序(ChIPseq)。我们预计，这个试点项目将产生第一个系统，定义亚核区是如何跨物种实时形成的，并为NIH R01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.