Ribosomal DNA and the Nucleolus as Keystones of Nuclear Architecture, Organization, and Function

The multicopy ribosomal DNA (rDNA) array gives origin to the nucleolus, a large nonmembrane-bound organelle that occupies a substantial volume within the cell nucleus. The rDNA/nucleolus has emerged as a coordinating hub in which seemingly disparate cellular functions converge, and from which a variety of cellular and organismal phenotypes emerge. However, the role of the nucleolus as a determinant and organizer of nuclear architecture and other epigenetic states of the genome is not well understood. We discuss the role of rDNA and the nucleolus in nuclear organization and function - from nucleolus-associated domains (NADs) to the regulation of imprinted loci and X chromosome inactivation, as well as rDNA contact maps that anchor and position the rDNA relative to the rest of the genome. The influence of the nucleolus on nuclear organization undoubtedly modulates diverse biological processes from metabolism to cell proliferation, genome-wide gene expression, maintenance of epigenetic states, and aging.