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 spa...

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Detalles Bibliográficos
Autores: Liang, Xue, Arrey, Gerard, Qin, Yating, Álvarez-González, Lucía|||0000-0001-8154-8614, Hariprakash, Judith Mary|||0000-0002-1164-347X, Ma, Jie, Holt, Sylvester|||0000-0002-9958-0169, Han, Peng|||0000-0002-3405-087X, Luo, Yonglun|||0000-0002-0007-7759, Li, Hanbo|||0000-0001-8778-9988, Ruiz Herrera Moreno, Aurora|||0000-0003-3868-6151, Pilegaard, Henriette|||0000-0002-1071-0327, Regenberg, Birgitte|||0000-0003-4996-7012
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:317813
Acceso en línea:https://ddd.uab.cat/record/317813
https://dx.doi.org/urn:doi:10.1038/s41467-025-57042-y
Access Level:acceso abierto
Palabra clave:Aging
Animals
Chromatin
DNA
Histones
Introns
Male
Mice
Mice, Inbred C57BL
Mutation
Transcription, Genetic
Descripción
Sumario: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.