EccDNA atlas in male mice reveals features protecting genes against transcription-induced eccDNA formation.

Xue Liang, Gerard Arrey, Yating Qin, Lucía Álvarez-González, Judith Mary Hariprakash, Jie Ma, Sylvester Holt, Peng Han, Yonglun Luo, Hanbo Li, Aurora Ruiz-Herrera, Henriette Pilegaard, Birgitte Regenberg

Section for Ecology and Evolution, Department of Biology, University of Copenhagen, Copenhagen, Denmark. · pubmed

Paper

Abstract

eccDNA is a driver of many cancers and a potential intermediate in other age-related disorders. However, little is known about the mechanisms underlying eccDNA formation in healthy tissue and how aging affects these processes. Here, we present an atlas of eccDNA across seven tissues of male mice spanning four ages. EccDNA correlates with open chromatin characterized by signatures of H3K27ac and H3K4me1. Additionally, the mutational load of eccDNA on genes correlates with tissue-specific transcription and increases logarithmically as a function of transcript level. Still, a population of intron-dense genes with many splice forms remains sheltered from eccDNA formation. We also find that the total number of eccDNA molecules does not increase as mice age, unlike other types of mutations. Our data reveal a link between eccDNA formation and transcript level that may drive gene architecture in mammals.

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Research summary

The paper claims that the formation of eccDNA is linked to transcript levels and that certain gene architectures are protected from eccDNA formation. This research is relevant as it explores the mechanisms of eccDNA formation in the context of aging, which could provide insights into age-related disorders and the underlying processes of aging itself.

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