Nucleolar Dominance

Abstract

Nucleolar dominance is an epigenetic phenomenon that describes the formation of nucleoli, the sites of ribosome assembly, by chromosomes inherited from only one parent/progenitor of a genetic hybrid. Nucleolus formation is programmed by chromosomal loci, known as nucleolus organiser regions (NORs), that are composed of ribosomal RNA (rRNA) genes repeated in long tandem arrays. Only transcriptionally active rRNA genes give rise to nucleoli, thus the molecular basis for nucleolar dominance is differential rRNA gene expression. Differential rRNA gene expression results from selective silencing of specific subsets of rRNA genes via changes in DNA methylation and histone posttranslational modifications. Because rRNA genes are nearly identical in sequence, it has long been a mystery how rRNA genes destined for silencing can be discriminated from genes that remain active. Recent genetic evidence indicates that selective rRNA gene silencing results from inactivation of whole NORs, not mechanisms that discriminate between individual rRNA genes.

Key Concepts

  • In genetic hybrids, rRNA genes inherited from the different parents, or progenitors, can be differentially expressed.
  • Specific subsets of rRNA genes are also differentially expressed in pure species (nonhybrids).
  • Nucleolar dominance is a manifestation of a dosage control system that operates in all eukaryotes to control the number of active rRNA genes.
  • Nucleolar dominance in both hybrids and pure species involves the selective silencing of ribosomal RNA gene loci, known as nucleolus organiser regions, that span millions of base pairs.
  • Ribosomal RNA gene silencing involves cytosine methylation and repressive histone posttranslational modifications.
  • Genetic evidence indicates that selective rRNA gene silencing results from inactivation of entire nucleolus organiser regions (NORs) rather than silencing decisions that are made one rRNA gene at a time.

Keywords: chromatin modification; DNA methylation; epigenetic phenomena; gene silencing; nucleolus organiser region; ribosomal RNA; RNA polymerase I; chromosome position effect

Figure 1. Cartoon depicting the discovery of nucleolar dominance based on observations of metaphase chromosomes in pure species and interspecific hybrids. Haploid chromosome sets of two progenitor species, each with three chromosomes, and their diploid hybrid are depicted. Species A and B each have a chromosome with an NOR that forms a secondary constriction at metaphase as a consequence of rRNA gene transcription during the preceding interphase and persistent binding of transcription factors that interfere with chromosome condensation. In hybrids, secondary constrictions observed only on the NOR‐bearing chromosome(s) of one progenitor reflect the differential expression of rRNA genes at different NORs.
Figure 2. Relationship between the nucleolus, NOR and rRNA gene repeats. The nucleolus fully forms during interphase, but its remnant persists in association with secondary constrictions at NORs during metaphase. NORs are the chromosomal loci where the rRNA genes transcribed by DNA‐dependent RNA polymerase I (Pol I) are tandemly repeated in hundreds of copies. Each Pol I transcription unit includes the 18S, 5.8S and 25–28S rRNA sequences assembled within the ribosomes, and is separated from the next gene by an intergenic spacer that includes the promoter and other regulatory elements important for transcriptional regulation.
Figure 3. Molecular attributes of the rRNA gene ‘on’ and ‘off’ states in the plant genus, Arabidopsis. Silencing in the allotetraploid A. suecica involves components of the RNA‐directed DNA methylation pathway and repressive histone posttranslational modifications typical of condensed heterochromatin. By contrast, the active state is characterised by histone posttranslational modifications typical of decondensed euchromatin and cytosine hypomethylation.
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Pikaard, Craig S(Apr 2018) Nucleolar Dominance. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005976.pub3]