257-LB: Defining the Stage-Dependent Transcriptome and Methylome in the Mouse Liver during Perinatal Metabolic Maturation

Abstract

A mammalian liver serves as an extramedullary hematopoietic organ during fetus, and matures into a metabolic organ after birth, thereby adapting to the changes in nutritional environment. PPARα-dependent DNA demethylation upregulates hepatic fatty acid β-oxidation (FAO) genes in the postnatal mouse liver to produce energy from breast milk lipids. However, the detailed interaction between DNA methylation (DNAme) and gene expression in the liver through perinatal stages remain poorly understood. Here, we perform an integrative analysis of transcriptome and methylome of the mice liver at fetal, neonatal, and postweaning stages. While the level of global DNAme gradually increased from fetal to postweaning stages, we found a drastic loss of DNAme in specific regions that are associated with metabolic pathways such as FAO, gluconeogenesis, and amino acid metabolism within the neonatal stage in concordance with the activation of such metabolic processes. Moreover, in silico analysis predicted transcription factors, such as HNF4α, PPARα, NR1H2, and NR1H3, as key epigenetic regulators within lactation period. We also observed an inactivation of erythrocyte development with a concordant gain of DNAme. This analysis extends the epigenetic landscape for understanding the hepatic maturation during early life, and suggests the importance of lactation period in epigenetic regulation. Disclosure S. Yano: None. N. Sato: None. H. Araki: None. F. Miura: None. T. Ito: None. Y. Ogawa: None.