The Epiallelic Nature of Mouse Ribosomal DNA

Ribosomal DNA (rDNA) displays substantial inter-individual genetic variation in human and mouse. Here we report that 45S rDNA units in the C57BL/6J mouse strain are epiallelic, existing as distinct genetic haplotypes that influence the epigenetic state and transcriptional output of any given unit. Epigenetic dynamics at these haplotypes are dichotomous and lifestage specific: at one haplotype, the DNA methylation state is sensitive to the in utero environment, but refractory to post-weaning influences, whereas other haplotypes entropically gain DNA methylation during ageing only. rDNA epiallelism is influenced by total rDNA copy number, and also found in other inbred mouse strains and humans. In the future, it will be important to consider the impact of inter-individual rDNA (epi)genetic variation on mammalian phenotypes and diseases. ### Competing Interest Statement The authors have declared no competing interest.