Nuclear compartments, genome folding, and enhancer-promoter communication

The eukaryotic genome has an extremely complex spatial organization. The physical distances between regulatory elements of the genome, such as enhancers, promoters, insulators, and CpG-islands, do not necessarily reflect genomic distances. Some remote regulatory elements appear to interact physically with target promoters in the 3D nuclear space. These spatial contacts are thought to play a crucial role in the regulation of transcription. Recent studies performed using 3C (chromosome conformation capture)-based methods, FISH (fluorescence in situ hybridization) coupled with confocal microscopy, and other experimental approaches have revealed that the spatial interactions of distant genomic elements within a folded chromosome are specific and functionally relevant. Additionally, the spatial organization of the eukaryotic genome is linked to the functional compartmentalization of the cell nucleus. In this review, we discuss the current state of research on the functional architecture of the eukaryotic genome. Special emphasis is given to the role of the spatial organization of the genome in establishing communication between enhancers and promoters. The driving forces of the juxtaposition of remote genomic elements are also considered.