Genomic domains and regulatory elements operating at the domain level.

The sequencing of the complete genomes of several organisms, including humans, has so far not contributed much to our understanding of the mechanisms regulating gene expression in the course of realization of developmental programs. In this so-called "postgenomic" era, we still do not understand how (if at all) the long-range organization of the genome is related to its function. The domain hypothesis of the eukaryotic genome organization postulates that the genome is subdivided into a number of semiindependent functional units (domains) that may include one or several functionally related genes, with these domains having well-defined borders, and operate under the control of special (domain-level) regulatory systems. This hypothesis was extensively discussed in the literature over the past 15 years. Yet it is still unclear whether the hypothesis is valid or not. There is evidence both supporting and questioning this hypothesis. The most conclusive data supporting the domain hypothesis come from studies of avian and mammalian beta-globin domains. In this review we will critically discuss the present state of the studies on these and other genomic domains, paying special attention to the domain-level regulatory systems known as locus control regions (LCRs). Based on this discussion, we will try to reevaluate the domain hypothesis of the organization of the eukaryotic genome.