Linking Maintenance of Chromosome Structure to Transcriptional Regulation

描述（申请人提供）：细胞中基因表达的精确调控是一项重要的任务，只有通过多种分子途径的协调才能完成。其中一条途径涉及到染色体结构成分对转录的调节。染色体结构的异常控制与多种发育综合征、畸形和肿瘤的进展有关，这是由于基因的错误调节。最近的证据表明，在增强子环介导的转录过程中，染色体结构通过DNA环的形成将增强子带到启动子附近，从而与基因表达联系起来。干细胞是一种理想的细胞类型，因为它们具有独特的能力，可以分化成生物体的任何细胞类型，也可以自我更新。为了研究调控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。本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体）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，我们将确定负责凝缩蛋白募集和分布的因素。我们将研究凝缩蛋白与其他已知转录装置成员的全基因组占用模式，并将这种模式与基因表达数据联系起来。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，应该被认为是充分了解影响细胞中基因表达程序的各种过程之间相互作用的必要条件。

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.