Spatial Organization of Gene Expressoin

基因表达的空间组织

• 批准号: 7988882
• 负责人: DAVID L SPECTOR
• 金额: $ 9.51万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-17 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7988882
• 关键词: Address; Animals; Binding; Cell Nucleus; Cells; Chromatin; Chromatin Structure; Chromosome Territory; Cytoplasmic Granules; Development; Disease; Disease model; Event; Funding; Gene Expression; Gene Order; Gene Structure; Genes; Genetic; Genetic Transcription; Genome; Goals; Human; Imagery; In Vitro; Individual; Kinetics; Knock-in Mouse; Life; Mammalian Cell; Membrane; Messenger RNA; Mitosis; Molecular; Morphogenesis; Nuclear; Nuclear Pore Complex; Nuclear RNA; Nuclear Structure; Nucleoplasm; Organelles; Organism; Pathology; Phase; Physical condensation; Play; Positioning Attribute; Process; Proteins; RNA; RNA Polymerase II; RNA Processing; RNA Splicing; Regulation; Role; Series; Skin; Staging; System; Time; Tissues; Transcriptional Activation; Transcriptional Regulation; Transgenic Organisms; base; chromatin modification; daughter cell; human disease; in vivo; innovation; insight; mRNA Precursor; messenger ribonucleoprotein; molecular imaging; mouse model; particle; research study

DESCRIPTION (provided by applicant): The long-term goal of this project is to develop a complete understanding of the spatial and temporal events involved in the regulation of RNA polymerase II transcription and pre-mRNA processing in living cells. An understanding of these parameters in the context of the living cell and organism will provide the basis to identify changes in these events that occur in cells or tissues associated with various disease states. The short-term goals will utilize a previously developed live cell gene expression system to address how a specific genetic locus is modulated at the G2/M and M/G1 transitions in living cells. The spatial and temporal dynamics of factors involved in gene expression will be examined as well as how the transcriptional status of a gene is transmitted to daughter cells during mitosis. In addition, this system will be used to study critical unanswered questions relating to where and when components of the mRNP export machinery associate with nascent mRNPs and how mRNPs are transported through the nuclear pore complex in human cells. Finally, a series of highly innovative experiments will be initiated to bring real-time gene expression studies into the context of a living animal in order to study tissue specific dynamics and changes in gene expression upon skin differentiation. This approach will provide significant insight into gene expression within a tissue and allow one to directly access nuclear dynamics in the context of differentiation and morphogenesis in vivo. Together, these studies will provide significant insight into our understanding of the functional organization of the nucleus with regard to gene expression. Aberrations in nuclear organization have the potential to result in alterations in gene expression, the end product of which may be one of the many pathologies associated with human disease. These studies will bring us a major step closer to studying and evaluating disease models by in vivo molecular imaging and dynamics.

描述（由申请人提供）：该项目的长期目标是全面了解活细胞中 RNA 聚合酶 II 转录和前 mRNA 加工调节所涉及的空间和时间事件。在活细胞和生物体的背景下了解这些参数将为识别与各种疾病状态相关的细胞或组织中发生的这些事件的变化提供基础。短期目标将利用先前开发的活细胞基因表达系统来解决活细胞中 G2/M 和 M/G1 转变时如何调节特定基因位点的问题。将检查参与基因表达的因素的空间和时间动态，以及基因的转录状态如何在有丝分裂过程中传递给子细胞。此外，该系统将用于研究有关 mRNP 输出机制的组件何时何地与新生 mRNP 关联以及 mRNP 如何通过人体细胞核孔复合体转运的关键未解答问题。最后，将启动一系列高度创新的实验，将实时基因表达研究带入活体动物的背景中，以便研究皮肤分化时组织特异性动态和基因表达的变化。这种方法将提供对组织内基因表达的重要洞察，并允许人们在体内分化和形态发生的背景下直接了解核动力学。总之，这些研究将为我们理解细胞核在基因表达方面的功能组织提供重要的见解。核组织的畸变有可能导致基因表达的改变，其最终产物可能是与人类疾病相关的多种病理学之一。这些研究将使我们在通过体内分子成像和动力学研究和评估疾病模型方面迈出重要一步。