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 and Birgitte Regenberg ()
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Xue Liang: University of Copenhagen
Gerard Arrey: University of Copenhagen
Yating Qin: University of Copenhagen
Lucía Álvarez-González: Universitat Autònoma de Barcelona
Judith Mary Hariprakash: University of Copenhagen
Jie Ma: BGI Research
Sylvester Holt: University of Copenhagen
Peng Han: University of Copenhagen
Yonglun Luo: Aarhus University
Hanbo Li: BGI Research
Aurora Ruiz-Herrera: Universitat Autònoma de Barcelona
Henriette Pilegaard: University of Copenhagen
Birgitte Regenberg: University of Copenhagen

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-57042-y

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