Nucleolar dominance is a phenomenon in plant and animal hybrids whereby one parental set of ribosomal RNA (rRNA) genes is transcribed, but the hundreds of rRNA genes inherited from the other parent are silent. The phenomenon gets it name because only transcriptionally active rRNA genes give rise to a nucleolus, the site of ribosome assembly. Nucleolar dominance provided the first clear example of DNA methylation and histone deacetylation acting in partnership in a gene-silencing pathway. However, the sites of chromatin modification and the ways in which one set of rRNA genes are targeted for repression remain unclear. Another unresolved question is whether the units of regulation are the individual rRNA genes or the multi-megabase chromosomal domains that encompass the rRNA gene clusters.