Regulating retinal gene expression in three-dimensional nuclear space

调控三维核空间中的视网膜基因表达

• 批准号: 8699920
• 负责人: XIANGYUN WEI
• 金额: $ 23.03万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8699920
• 关键词: 3-Dimensional; Affect; Age related macular degeneration; Architecture; Archives; Area; Base Sequence; Biochemical; Biological Models; Cell Culture System; Cell Nucleus; Cells; Cessation of life; Chromatin; Chromosomes; Cone; DNA; Degenerative Disorder; Development; Disease; Ensure; Epigenetic Process; Equilibrium; Fluorescent in Situ Hybridization; Foundations; Future; Gene Cluster; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Gene Order; Gene Structure; Generations; Genes; Genetic; Genetic Transcription; Genome; Genomic Instability; Genomics; Health; Individual; Investigation; Knowledge; Maps; Modeling; Nuclear; Nuclear Structure; Outcome; Photoreceptors; Phototransduction; Play; Positioning Attribute; Progeria; Public Health; Regulation; Research; Retina; Retinal; Retinal Cone; Retinal Degeneration; Retinal Dystrophy; Retinal Photoreceptors; Role; Testing; Time; Variant; Vertebrates; Zebrafish; cancer type; cell type; gene function; in vivo; preference; prevent; public health relevance; retinal rods; spatial relationship

DESCRIPTION (provided by applicant): Growing evidence demonstrates the essentiality of the dynamic and nonrandom 3-dimensional (3D) organization of the genome in balancing gene transcription. Gene expression needs to be balanced at quantitative levels because imbalanced gene expression leads to a biochemical imbalance in the cells, which eventually leads to cellular damages or even death. In fact, it was recently found that age-related macular degeneration (AMD) severely disrupts the balance of gene expression. In addition, abnormalities in nuclear architecture have been observed to be involved in genomic instability and imbalanced gene expression in progeria and various types of cancer. Despite the recent progress, we still have much to understand about how chromatin organization is dynamically regulated as well as how such regulations are required to ensure quantitatively balanced gene expression. In an effort to help close this knowledge gap, we here propose to map the 3D positions of some representative genes of different expression levels and functions in the cone photoreceptor nuclei in the zebrafish retina. These mapping studies will reveal functional relationships between the expression activities of these genes and their spatial positioning in photoreceptor nuclei. The aim of this proposal is to determine at the global level how the 3D nuclear architecture of cone cells is organized to facilitate selective and quantitatively balanced gene expression. The results of this research will establish a foundation for future research to achieve our long term objective to understand how the nuclear architecture plays a role in maintaining retinal health as well as preventing retinal degeneration by balancing retinal gene expression.

描述（由申请人提供）：越来越多的证据表明基因组的动态和非随机三维（3D）组织在平衡基因转录中的重要性。基因表达需要在定量水平上平衡，因为不平衡的基因表达会导致细胞中的生化失衡，最终导致细胞损伤甚至死亡。事实上，最近发现年龄相关性黄斑变性（AMD）严重破坏了基因表达的平衡。此外，已观察到核结构的异常涉及早衰症和各种类型癌症中的基因组不稳定性和不平衡的基因表达。尽管最近的进展，我们仍然有很多了解染色质组织是如何动态调节，以及如何需要这样的规定，以确保定量平衡的基因表达。为了帮助缩小这一知识差距，我们在这里提出了一些代表性的基因在斑马鱼视网膜的视锥细胞核中的不同表达水平和功能的3D位置。这些定位研究将揭示这些基因的表达活动和它们在感光细胞核中的空间定位之间的功能关系。的 该提案的目的是在全球水平上确定视锥细胞的3D核结构如何组织以促进选择性和定量平衡的基因表达。结果 本研究将为未来的研究奠定基础，以实现我们的长期目标 了解细胞核结构如何在维持视网膜健康以及通过平衡视网膜基因表达来预防视网膜变性方面发挥作用。