Stability of Genomic Imprinting and X-Chromosome Inactivation in the Aging Brain

• DOI: 10.1101/2023.09.29.560184
• Publication Date: 2023-10-01T04:55:12Z
• Authors: Samantha Mancino; Janith Seneviratne; Annalisa Mupo; Felix Krueger; David Oxley; Melanie A Eckersl...; Simão Teixeira da...
• Keywords: Genomic Imprinting; Imprinting (psychology); Angelman Syndrome

Abstract Epigenetic drift is a hallmark of aging that contributes to the irreversible decline in organismal fitness ultimately leading aging-related diseases. modifications regulate cellular memory epigenetic processes genomic imprinting and X-chromosome inactivation ensure monoallelic expression imprinted X-linked genes. Whether affects maintenance has not been comprehensively studied. Here, we investigate allele-specific transcriptional signatures brain, by comparing juvenile old hybrid mice obtained from C57BL/6J (BL6) & CAST/EiJ (CAST) reciprocal crosses, with an emphasis on hippocampus (HCP). We confirm aged HCP shows increase DNA hydroxymethylation, sign drift, typical signature. Genomic was found be largely unaffected stable parent-of-origin-specific methylation HCP, but also other brain regions such as cerebellum (CB), nucleus accumbens, hypothalamus prefrontal cortex. Consistently, transcriptomics analysis confirmed unaltered HCP. An exception are three novel non-coding transcripts ( B230209E15Rik , Ube2nl A330076H08Rik ) at Prader-Willi syndrome/Angelman syndrome (PWS/AS) locus which lose strict during aging. Like imprinting, remarkably no signs aging-driven skewing or relaxation Our study provides valuable resource for evaluating reveals that, despite aging, remain predominantly throughout process physiological mouse brain.