The study of chromosome, and genome, organization is a both an ongoing challenge, and one with a long history. Following the advent of high-throughput sequencing and genomic technologies, much research has focused on the one-dimensional, or sequence-level, organization of genomes, with many successes. Nonetheless, genomes are physically organized as chromosomes in the three-dimensional confines of the cell nucleus, with implications for processes including gene regulation, DNA replication, and cell division.