The cell nucleus in humans and other higher organisms is filled with chromatin, the protein-DNA complex in which the genome is packaged. However, the arrangement of chromatin within the nucleus is not random. Entire specific regions of the genome are localized near the nuclear periphery; others are sequestered in "organelles" such as the nucleolus. In each case, the location may control the activity of the gene. Certain chromosomes contain genes that control sex-specific features of the organism. Genes on these chromosomes may be specifically silenced or activated by structures that propagate and extend over the entire chromosome. It has been known for a long time that the expression of genes is controlled by DNA sequence elements located close to the genes themselves. However, striking results obtained over the last several years show that important contributions to this regulation are also made by DNA sequences far away from the target gene: within the nucleus, distant sites on chromatin make many specific and preferred long-range contacts. Many of these are associated with previously unsuspected regulatory pathways. All these results lead to a revised view of the nucleus, which contains both complex networks of interacting sites and highly organized substructures.