TY - JOUR
T1 - EccDNA atlas in male mice reveals features protecting genes against transcription-induced eccDNA formation
AU - Liang, Xue
AU - Arrey, Gerard
AU - Qin, Yating
AU - Álvarez-González, Lucía
AU - Hariprakash, Judith Mary
AU - Ma, Jie
AU - Holt, Sylvester
AU - Han, Peng
AU - Luo, Yonglun
AU - Li, Hanbo
AU - Ruiz-Herrera, Aurora
AU - Pilegaard, Henriette
AU - Regenberg, Birgitte
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/2/22
Y1 - 2025/2/22
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85218487594
UR - https://www.mendeley.com/catalogue/5d6b4477-2556-3d5f-a8d0-b250bbc7c084/
UR - https://portalrecerca.uab.cat/en/publications/843aae84-3374-4122-b43c-ce2289cde74d
U2 - 10.1038/s41467-025-57042-y
DO - 10.1038/s41467-025-57042-y
M3 - Article
C2 - 39984484
AN - SCOPUS:85218487594
SN - 2041-1723
VL - 16
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1872
ER -
