Dynamic patterns of histone methylation are associated with ontogenic expression of the Cyp3a genes during mouse liver maturation

Human cytochrome P450 3A (CYP3A) members are major drug-metabolizing enzymes in the liver. Two genes, CYP3A4 and CYP3A7, exhibit a developmental switch in gene expression during liver maturation. CYP3A4 is mainly expressed in adults, whereas CYP3A7 is dominantly expressed during the fetal and neonatal stages. Their ontogenic expression results in devel-opmentally related changes in the capacity to metabolize en-dogenous and exogenous compounds. Thus, it is desirable to understand the mechanisms controlling the developmental switch. Mice also exhibit a developmental switch between Cyp3a16 (neonatal isoform) and Cyp3a11 (adult isoform) and may serve as a model to study the mechanisms controlling the developmental switch. Because the epigenetic code (e.g., DNA methylation and histone modifications) is implicated in regulat