Work

Intraindividual rDNA copy number variation and methylation in humans

Year: 2025

Type: article

Abstract: The absolute number of rDNA transcription units (TU) can vary by about one order of ten among individuals. Apart from extensive rDNA copy number (CN) variation and instability in many cancers, there is little information on the extent of intraindividual CN variation between normal tissues. Here we used droplet digital PCR and deep bisulfite sequencing to determine both the absolute rDNA CN and the number of presumably active CN with a hypomethylated (≤10 %) promoter region in up to six different tissues of 13 autopsy probands. In general, the absolute rDNA CN as well as the frequency of the minor A variant were highly similar between tissues (cerebellum, cerebrum, colon, heart, intestine, kidney, liver, and spleen) of the same individual. However, in some probands absolute CN in one or multiple tissues was much higher than in the other tissues, indicative of relaxation/breakdown of the CN control system. The amplified copies were inactivated by promoter methylation and, thus, the number of active CN was largely independent from absolute CN. Collectively, our data suggest that with some notable exceptions absolute and even more active rDNA CN are maintained during development and differentiation in different tissues of the same individual. Despite the low intraindividual variation active CN appeared to systematically vary between tissues. Cerebellum and cerebrum consistently exhibited lower active CN than the other analyzed tissues. We estimate that >50 active rDNA TU are required for normal tissue/organ function. • Both absolute and active (hypomethylated) rDNA copy number (CN) are generally similar across tissues within an individual. • Despite low intraindividual variation active rDNA CN differ between tissues. • At least 50 active (hypomethylated) rDNA copies may be required for normal tissue/organ function. • Relaxation/breakdown of the CN control system may occur in one or several tissues. • As a compensation mechanism excess rDNA copies are inactivated by promoter methylation.

Source: Experimental Cell Research

DOI: 10.1016/j.yexcr.2025.114793

Authors: Jana Durackova, Ramya Potabattula, Andreas Rosenwald, Thomas Haaf

Institution: University of Würzburg

Language: English

Topic: Chromosomal and Genetic Variations

Subfield: Plant Science

Field: Agricultural and Biological Sciences

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,270