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The vast majority of DNA sequences in the human genome are never expressed. More than 95% of sequences do not encode genes and only a subset of the 40,000 or so genes is expressed at any given time. The topological organization of chromosomes and genomes is a potential regulatory mechanism to ensure efficient and coordinated expression of sets of genes. For example, spatially segregation of inactive genes from active genes, or exposing genes to a nuclear region with a high concentration of particular regulatory factors, can result in altered gene expression. In order to understand how genomes function in vivo, a number of very fundamental questions concerning the topology of genomes and the role genome topology plays in gene expression must be resolved: Are chromosomes arranged randomly within the nucleus? How does genome topology affect gene expression and regulation? What are the dynamic aspects of genome organization in-vivo? We are currently using chromosome painting techniques, in-situ hybridization methods and 3D-reconstruction techniques to address these issues.
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