Dynamic DNA and histone methylation influences the ontogeny of xenobiotic metabolizing genes during postnatal mouse liver maturation

Abstract

After birth, liver transitions from hematopoiesis to meet new metabolic demands, including xenobiotic (drug) processing. During this maturation, expression of many xenobiotic processing genes increases in distinct patterns. Since the epigenetic code is implicated in regulating gene expression and cellular differentiation during development, we hypothesized that these mechanisms may also be involved in the ontogenic expression of xenobiotic processing genes. In the current study, ChIP‐on‐chip assays representing 14% of the mouse genome were used to define the levels and distributions of DNA methylation (meDNA), histone 3 lysine 4 dimethylation (H3K4me2), and histone 3 lysine 27 trimethylation (H3K27me3) during postnatal liver development. In addition to the epigenetic data, gene expression microarrays defined ontogenic expression patterns. meDNA was not observed in the examined xenobiotic processing genes. Gradual increases in H3K4me2 from prenatal to adult ages were observed in several xenobiotic processing genes (e.g. Cyp3a11 and Cyp2d22). Higher levels of H3K27me3 in prenatal liver coincided with the suppression of gene expression of some xenobiotic processing genes at that age (e.g. Cyp3a16). In conclusion, these data suggest that the epigenetic code is involved in the functional transition of the postnatal liver. This work was supported by National Institute of Health Grant 5P20 RR021940.