EccDNA atlas in male mice reveals features protecting genes against transcription-induced eccDNA formation
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.
Authors
- Peng Han (ORCID: https://orcid.org/0000-0002-3405-087X)
- Judith Mary Hariprakash (ORCID: https://orcid.org/0000-0002-1164-347X)
- Gerard Arrey (ORCID: https://orcid.org/0000-0003-2055-5479)
- Aurora Ruiz‐Herrera (ORCID: https://orcid.org/0000-0003-3868-6151)
- Yonglun Luo (ORCID: https://orcid.org/0000-0002-0007-7759)
- Henriette Pilegaard (ORCID: https://orcid.org/0000-0002-1071-0327)
- Yating Qin (ORCID: https://orcid.org/0000-0001-8024-3210)
- Sylvester Holt (ORCID: https://orcid.org/0000-0002-9958-0169)
- Birgitte Regenberg (ORCID: https://orcid.org/0000-0003-4996-7012)
- Xue Liang (ORCID: https://orcid.org/0000-0001-6864-7386)
- Hanbo Li (ORCID: https://orcid.org/0000-0001-8778-9988)
- Lucía Álvarez-González (ORCID: https://orcid.org/0000-0001-8154-8614)
- Jie Ma (ORCID: https://orcid.org/0000-0003-0648-9786)
Institutions
- Universitat Autònoma de Barcelona (ES)
- University of Copenhagen (DK)
- Aarhus University (DK)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-02-21
- DOI
- https://doi.org/10.1038/s41467-025-57042-y
- Citations
- 10
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 9.36
Funders
- European Commission
- Ministerio de Economía y Competitividad
- Institució Catalana de Recerca i Estudis Avançats
- Novo Nordisk
- Ministerio de Ciencia e Innovación
- Novo Nordisk Fonden
- Agència de Gestió d'Ajuts Universitaris i de Recerca