Linking Maintenance of Chromosome Structure to Transcriptional Regulation

将染色体结构的维持与转录调控联系起来

• 批准号: 8658812
• 负责人: Jill Dowen
• 金额: $ 5.7万
• 依托单位: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8658812
• 关键词: Area; Cell Maintenance; Cells; ChIP-seq; Chromatin; Chromatin Loop; Chromosome Structures; Chromosomes; DNA Packaging; Data; Defect; Deformity; Development; Enhancers; Gene Expression; Gene Expression Regulation; Genes; Genetic Enhancer Element; Genetic Transcription; Genome; Genomics; High-Throughput Nucleotide Sequencing; Lead; Link; Maintenance; Malignant Neoplasms; Maps; Mediating; Methodology; Mitosis; Modeling; Molecular; Organism; Pathway interactions; Pattern; Play; Process; Proteins; Research; Role; Site; Stem cells; Structure; Syndrome; Technology; Transcriptional Regulation; base; cell type; chromatin immunoprecipitation; cohesin; condensin; design; embryonic stem cell; genome-wide; interest; member; programs; promoter; protein complex; research study; self-renewal; tumor progression

DESCRIPTION (provided by applicant): The precise regulation of gene expression in the cell is an important task only accomplished by the coordination of multiple molecular pathways. One of these pathways involves the regulation of transcription by chromosome structural components. Aberrant control of chromosome structure is associated with a variety of developmental syndromes, deformities, and the progression of tumors due to the misregulation of genes. Recent evidence has linked chromosome structure to gene expression via the formation of DNA loops that bring enhancers in proximity to promoters during enhancer-loop-mediated transcription. Stem cells represent an ideal cell type to dissect transcriptional regulation due to their unique abilities to differentiate into any cell type of an organism, and alo self-renew. To study the molecular processes regulating transcription of the genome we will employ high-throughput genomic-based technologies and methodologies. The objective of this proposed research is to understand the role of Condensin, a protein complex required for the structural maintenance of chromosomes, in mediating transcription. We will map the distribution of Condensin on the genome and we will identify factors responsible for recruitment and distribution of Condensin. We will examine the pattern of genome-wide occupancy of Condensin with other known members of the transcriptional apparatus and also correlate this pattern with gene expression data. Uncovering the function of chromosome structure in transcription remains a largely unexplored area of research and should be considered essential in fully appreciating the interplay between the various processes that influence gene expression programs in the cell.

描述（申请人提供）：细胞内基因表达的精确调控是一项必须通过多种分子途径协调才能完成的重要任务。这些途径之一涉及染色体结构成分的转录调节。由于基因的错误调节，染色体结构的异常控制与多种发育综合征、畸形和肿瘤进展有关。最近的证据表明，通过形成 DNA 环，在增强子环介导的转录过程中，使增强子靠近启动子，从而将染色体结构与基因表达联系起来。干细胞代表了剖析转录调控的理想细胞类型，因为它们具有分化为生物体任何细胞类型的独特能力，并且具有自我更新能力。为了研究调节基因组转录的分子过程，我们将采用基于高通量基因组的技术和方法。这项研究的目的是了解凝缩蛋白（一种维持染色体结构所需的蛋白质复合物）在介导转录中的作用。我们将绘制凝缩蛋白在基因组上的分布图，并确定负责凝缩蛋白招募和分布的因素。我们将检查凝缩蛋白与转录装置的其他已知成员的全基因组占据模式，并将该模式​​与基因表达数据相关联。揭示染色体结构在转录中的功能仍然是一个很大程度上未被探索的研究领域，并且应该被认为对于充分理解影响细胞中基因表达程序的各种过程之间的相互作用至关重要。