Premium
Dynamic patterns of histone methylation are associated with ontogenic expression of the Cyp3a genes during mouse liver maturation
Author(s) -
Li Ye,
Yue Cui,
Hart Steven N,
Klaassen Curtis D
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.752.5
Subject(s) - cyp3a , biology , epigenetics , locus (genetics) , histone , dna methylation , gene , gene expression , regulation of gene expression , histone h3 , genetics , cytochrome p450 , metabolism , endocrinology
Human cytochrome P450 3A members, CYP3A4 and CYP3A7, exhibit a developmental switch in gene expression during liver maturation. This developmental switch results in the variation of drug metabolism between children and adults. Mouse Cyp3a11 and Cyp3a16 are orthologous to CYP3A4 and CYP3A7 respectively. They also exhibit a similar developmental switch and may serve as a model to study human CYP3A switch. Since epigenetic mechanisms are implicated in gene expression and cellular differentiation during development, we hypothesized that they may be involved in controlling the developmental switch of Cyp3a genes. The current study determined the status of DNA methylation, histone 3 lysine 4 dimethylation (H3K4me2), and histone 3 lysine 27 trimethylation (H3K27me3) around the mouse Cyp3a locus by ChIP‐chip assays in mice livers at various developmental ages. DNA was not hypermethylated in the Cyp3a locus across from prenatal to adult stages. However, increases in Cyp3a11 expression in livers from perinatal to adult ages were associated with increases of H3K4me2 around Cyp3a11 gene. Suppression of Cyp3a16 expression in adult mice coincided with the decrease of H3K4me2 and increase of H3K27me3 around Cyp3a16. In conclusion, H3K4me2 and H3K27me3 are dynamically changed in a locus‐specific manner along the Cyp3a locus during liver maturation, and involved in the regulation of the developmental switch of Cyp3a genes.