Chromosome-specific epigenetic control and transmission of ribosomal DNA arrays in Hominidae genomes
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.
Authors
- Chongbei Zhao (ORCID: https://orcid.org/0000-0002-7224-5600)
- Erik Garrison (ORCID: https://orcid.org/0000-0003-3821-631X)
- Jennifer L. Gerton (ORCID: https://orcid.org/0000-0003-0743-3637)
- Dmitry Antipov (ORCID: https://orcid.org/0000-0002-6087-0660)
- Andrea Guarracino (ORCID: https://orcid.org/0000-0001-9744-131X)
- Tamara Potapova (ORCID: https://orcid.org/0000-0003-2761-1795)
- Karen H. Miga (ORCID: https://orcid.org/0000-0002-3670-4507)
- Sean McKinney (ORCID: https://orcid.org/0000-0002-9740-6247)
- Sophie Hoffman (ORCID: https://orcid.org/0000-0003-2518-6422)
- Leonardo Gomes de Lima (ORCID: https://orcid.org/0000-0001-6340-6065)
- Monika Čechová (ORCID: https://orcid.org/0000-0002-7420-2663)
- Steven J. Solar (ORCID: https://orcid.org/0000-0003-3051-9009)
- Arang Rhie (ORCID: https://orcid.org/0000-0002-9809-8127)
- Matthew Borchers (ORCID: https://orcid.org/0000-0001-5903-3489)
- Alexander Gogol (ORCID: https://orcid.org/0000-0003-1972-4124)
- Adam M. Phillippy (ORCID: https://orcid.org/0000-0003-2983-8934)
- Yan Wang (ORCID: https://orcid.org/0000-0001-7689-4942)
- Mark Mattingly (ORCID: https://orcid.org/0009-0000-6139-9789)
- Paxton Kostos
- Graciela Monfort Anez
- Kate Hall
- Jeff Haug
Institutions
- Stowers Institute for Medical Research (US)
- National Institutes of Health (US)
- University of Tennessee Health Science Center (US)
- University of California, Santa Cruz (US)
- Masaryk University (CZ)
- Wellcome Sanger Institute (GB)
- National Human Genome Research Institute (US)
Publication Details
- Journal
- Cell Genomics
- Published
- 2025-10-04
- DOI
- https://doi.org/10.1016/j.xgen.2025.101031
- Citations
- 5
- Primary Topic
- Chromosomal and Genetic Variations
- Type
- article
- Field-Weighted Citation Impact
- 8.75
Funders
- National Institutes of Health