EccDNA atlas in male mice reveals features protecting genes against transcription-induced eccDNA formation
Liang, Xue (Qingdao-Europe Advanced Institute for Life Sciences. Lars Bolund Institute of Regenerative Medicine)
Arrey, Gerard (University of Copenhagen. Department of Biology)
Qin, Yating (Qingdao-Europe Advanced Institute for Life Sciences. Lars Bolund Institute of Regenerative Medicine)
Álvarez-González, Lucía (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Hariprakash, Judith Mary (University of Copenhagen. Department of Biology)
Ma, Jie (Qingdao-Europe Advanced Institute for Life Sciences. Lars Bolund Institute of Regenerative Medicine)
Holt, Sylvester (University of Copenhagen. Department of Biology)
Han, Peng (Qingdao-Europe Advanced Institute for Life Sciences. Lars Bolund Institute of Regenerative Medicine)
Luo, Yonglun (Aarhus University. Department of Biomedicine)
Li, Hanbo (Qingdao-Europe Advanced Institute for Life Sciences. Lars Bolund Institute of Regenerative Medicine)
Ruiz-Herrera Moreno, Aurora (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Pilegaard, Henriette (University of Copenhagen. Department of Biology)
Regenberg, Birgitte (University of Copenhagen. Department of Biology)

Date:	2025
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.
Grants:	European Commission 801199 Agencia Estatal de Investigación PID2020-112557GB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00122 Ministerio de Economía y Competitividad PRE-2018-083257
Note:	Altres ajuts: ICREA Academia
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Aging ; Animals ; Chromatin ; DNA ; Histones ; Introns ; Male ; Mice ; Mice, Inbred C57BL ; Mutation ; Transcription, Genetic
Published in:	Nature communications, Vol. 16 (February 2025) , art. 1872, ISSN 2041-1723

DOI: 10.1038/s41467-025-57042-y
PMID: 39984484

12 p, 2.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
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