Tamara Potapova, Paxton Kostos, Sean McKinney, Matthew Borchers, Jeff Haug, Andrea Guarracino, Steven J. Solar, Mark Mattingly, Graciela Monfort Anez, Leonardo Gomes de Lima, Yan Wang, Chongbei Zhao, Kate Hall, Alexander Gogol, Sophie Hoffman, Dmitry Antipov, Arang Rhie, Monika Čechová, Karen H. Miga, Erik Garrison, Adam M. Phillippy, Jennifer L. Gerton
Ribosomal RNA (rRNA) genes are organized in tandem arrays known as ribosomal DNA (rDNA) on multiple chromosomes in Hominidae genomes. We measured copy number and transcriptional activity status of rRNA gene arrays across multiple individual genomes, revealing an identifiable fingerprint of rDNA copy number and activity. In some cases, entire arrays were transcriptionally silent, characterized by high DNA methylation across the rRNA gene, inaccessible chromatin, and the absence of transcription factors and transcripts. Silent arrays showed reduced association with the nucleolus and decreased interchromosomal interactions, consistent with the model that nucleolar organizer function depends on transcriptional activity. Removing rDNA methylation activated silent arrays. Array activity status remained stable through induced pluripotent stem cell reprogramming and differentiation into cerebral and intestinal organoids. Haplotype tracing in two unrelated family trios showed paternal transmission of silent arrays. We propose that the epigenetic state buffers rRNA gene dosage, specifies nucleolar organizer function, and can propagate transgenerationally.