12246 The Stage-Dependent Transcriptome And Methylome Reveal Significance Of The Neonatal Period In Postnatal Metabolic Maturation Of The Mouse Liver

Abstract Disclosure: S. Yano: None. N. Sato: None. H. Araki: None. F. Miura: None. T. Ito: None. Y. Ogawa: None. The mammalian liver serves as an extramedullary hematopoietic organ during the fetus and matures into a metabolic organ after birth, adapting to changes in the nutritional environment. DNA demethylation upregulates fatty acid β-oxidation (FAO) genes in the postnatal mouse liver to produce energy from breast milk lipids. However, the detailed interactions between DNA methylation (DNAme) and gene expression through the perinatal stages remain poorly understood. Here, we perform an integrative analysis of the transcriptome and methylome of the mouse liver at the fetal, neonatal, and postweaning stages. We found a drastic loss of DNAme at the neonatal stage in specific regions associated with metabolic pathways such as FAO and gluconeogenesis in concordance with the activation of metabolic processes. Moreover, in silico analysis predicted transcription factors including HNF4α, PPARα, and NR1H2 as key epigenetic regulators within the neonatal period. We also observed an inactivation of erythrocyte development with a concordant gain of DNAme. This analysis extends the epigenetic landscape of postnatal hepatic maturation, suggesting the importance of the nutritional environment during the neonatal period for epigenetic regulation. Presentation: 6/3/2024