Chromosomal positioning and epigenetic architecture influence DNA methylation patterns triggered by galactic cosmic radiation

Abstract Despite surging interest in space travel in recent decades, the impacts of prolonged, elevated exposure to galactic cosmic radiation (GCR) on human health remain poorly understood. This form of ionizing radiation causes significant changes to biological systems including damage to DNA structure by altering epigenetic phenotype with emphasis on DNA methylation. Building on previous work by Kennedy et al. (2018), we evaluated spatial DNA methylation patterns triggered by high-LET (56Fe, 28Si) and low-LET (X rays) and the influence of chromosome positioning and epigenetic architecture in distinct radial layers of cell nucleus. Next, we validated our results using gene expression data of mice and JAXA astronauts. We showed that primarily 56Fe induces a persistent DNA methylation increase whereas 28Si and X rays induce a decrease DNA methylation which is not persistent with time. Moreover, we highlighted the role of heterochromatin-associated histone modifications in absorbing GCR and protecting euchromatin-associated DNA fragments localized in inner parts of nucleus. In summary, our study provides novel insights towards epigenetic nuclear architecture and its role in limiting external radiation damage.