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

• DOI: 10.59368/agingbio.20240030
• Publication Date: 2024-07-31T13:04:23Z
• Authors: Melanie A. Eckers...; Simão Teixeira da...; Samantha Mancino; Janith Seneviratne; Annalisa Mupo; Felix Krueger; David Oxley
• Keywords: Genomic Imprinting; Imprinting (psychology)

Changes in the epigenetic landscape are a hallmark of aging that contributes to irreversible decline organismal fitness ultimately leading aging-related diseases.Epigenetic modifications regulate cellular memory processes genomic imprinting and X-chromosome inactivation (XCI) ensure monoallelic expression imprinted X-linked genes.Whether aging-associated changes affect maintenance XCI 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 confirmed aged HCP showed expected increase DNA hydroxymethylation typical signature.Importantly, was largely unaffected, stable parent-of-origin-specific methylation multiple brain regions including HCP, cerebellum, nucleus accumbens, hypothalamus, prefrontal cortex.Consistently, transcriptomic bulk analysis unaltered HCP.An exception four novel non-coding transcripts (B230209E15Rik, Ube2nl, A330076H08Rik, A230057D06Rik) at Prader-Willi syndrome/Angelman syndrome locus, which lost strict during aging.Similar imprinting, remarkably no signs aging-driven skewing or relaxation genes.Our study provides valuable resource for evaluating reveals that, despite known occurring aging, remain predominantly throughout process physiological mouse brain.