Epigenetic Control of Ribosomal DNA Arrays Discovered

A groundbreaking study published in Cell Genomics reveals the discovery of epigenetic control of ribosomal DNA arrays in Hominidae genomes. The research, conducted at the Stowers Institute for Medical Research, demonstrates the significance of epigenetic state in buffering rRNA gene dosage, specifying nucleolar organizer function, and potentially propagating transgenerationally.

Key Takeaways:

• The study found that ribosomal RNA (rRNA) genes are organized in tandem arrays known as ribosomal DNA (rDNA) on multiple chromosomes in Hominidae genomes.
• The researchers 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.
• Silenced 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, suggesting that the epigenetic state buffers rRNA gene dosage.
• 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.
• The study proposes that the epigenetic state specifies nucleolar organizer function and can propagate transgenerationally.
• The research was conducted by Paxton Kostos and colleagues from the Stowers Institute for Medical Research.

Statistics:

• rRNA gene arrays were found to be organized in tandem arrays on multiple chromosomes in Hominidae genomes.
• The study analyzed copy number and transcriptional activity status of rRNA gene arrays across multiple individual genomes.
• DNA methylation levels were demonstrated to be high in transcriptionally silent arrays.
• Removing rDNA methylation activated silent arrays in 100% of cases (n=10).
• Array activity status remained stable through induced pluripotent stem cell reprogramming and differentiation into cerebral and intestinal organoids.

Sources:

• Paxton Kostos et al. (2025). Chromosome-specific epigenetic control and transmission of ribosomal DNA arrays in Hominidae genomes. Cell Genomics, 2025:101031.
• Research announcement published in Biotech Week, October 15, 2025, p 1568.