DNA methylation analysis of the Parkin gene in wild-type and TIGAR-deficient mouse tissues [EM-seq]
Parkin expression is persistently increased in TIGAR-deficient (TKO) mouse hearts, even after restoration of TIGAR expression in adulthood, suggesting a developmental epigenetic mechanism. To investigate whether DNA methylation contributes to this regulation, we performed whole-genome bisulfite sequencing (WGBS) on cardiac tissues from wild-type and TKO mice. RNA sequencing confirmed increased Parkin transcript levels across all exons in TKO hearts. WGBS analysis identified multiple differentially methylated regions (DMRs) across the Parkin gene body, with consistently lower methylation levels in TKO hearts. A prominent hypomethylated region was detected within intron 10, while no significant methylation changes were observed in the Parkin promoter CpG island. These data suggest that TIGAR deficiency is associated with stable, gene body–specific DNA methylation changes that correlate with increased Parkin expression. Overall design: Cardiac tissues were collected from wild-type and TIGAR-deficient (TKO) mice. Genomic DNA was isolated and analyzed by whole-genome bisulfite sequencing to assess DNA methylation patterns.