ABSTRACT

This chapter explores the development of molecular genomic approaches for mapping the structure of chromosomes, mainly based on chromosome conformation capture technology. It discusses the development and application of insights from the field of polymer physics to the problem of chromosome folding. The introduction of chromosome conformation capture in 2002 has revolutionized the study of the spatial organization of genomes by allowing mapping of three-dimensional chromosome structure at increasingly high resolution directly to sequence and at the scale of complete genomes. The size of genomes, and thus the number of possible chromatin interactions, makes chromosome conformation capture analysis using PCR impractical. Intra-chromosomal interactions tend to be much more frequent than inter-chromosomal interactions, even for loci separated by hundreds of megabases. The field of chromosome conformation analysis is experiencing a very exciting time of rapid gains in our knowledge of how genomes are organized in space and time and how this relates to regulation of genome function.