Recently, genomes have been recognized to adopt preferred physical architectures that are evolutionarily conserved and cell type specific. We developed a method for characterizing long-range inter- and intra- chromosomal interactions on a genome-wide scale. Our method is based on chromatin conformation capture (3C) but unlike 3C (or other derivative technologies), makes no a priori assumptions regarding interacting genetic elements. Due to the large size of mammalian genomes we initially validated our approach in haploid Saccharomyces cerevisiae. In this application we propose to use this method to understand the relationship between genome architecture and allele specific expression in mammalian development.
Very little is known about how cells interpret phenotype from genotype. One important waypoint in this interpretation is the establishment of cell-type specific genome topologies. We have developed a new method for characterizing the architecture of whole genomes. With further development we believe that our method will provide a physical annotation to cell state, and will fundamentally advance our understanding of cell biology.
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|Deng, Xinxian; Berletch, Joel B; Nguyen, Di K et al. (2014) X chromosome regulation: diverse patterns in development, tissues and disease. Nat Rev Genet 15:367-78|
|Witten, Daniela M; Noble, William Stafford (2012) On the assessment of statistical significance of three-dimensional colocalization of sets of genomic elements. Nucleic Acids Res 40:3849-55|