Expression of CYP2E1 during human fetal development: methylation of the CYP2E1 gene in human fetal and adult liver samples.

The expression and regulation of cytochrome P450IIE1 (CYP2E1) in adult and fetal human liver has been investigated. Three mRNA transcripts of 1.9, 2.7 and 3.8 kb were detected in all adult liver samples after hybridization with a full length cDNA to CYP2E1 whereas no expression was detected in 12 fetal liver samples studied. Similarly, expression of CYP2E1 was not detected in 11 placental samples (10-17 weeks gestational age) or in two full-term placental samples. CYP2E1 expression was not detected in fetal liver, kidney, lung, placenta (18 weeks gestational age) or liver (6 weeks gestational age) obtained at termination of pregnancy where maternal alcohol abuse had been established. Southern blot analysis of the cytosine methylation status of the CYP2E1 gene revealed substantial methylation of the 3' region of the gene in both adult and fetal human liver samples. No differences were observed in the methylation pattern of fetal liver samples between the gestational ages 12 and 17 weeks. Two small DNA fragments detected by the 5' end of the CYP2E1 cDNA were cleaved by the restriction enzyme HpaII in adult liver DNA but not in the fetal liver DNA samples. Methylation of specific 5' residues in the CYP2E1 gene may be responsible for the lack of transcription of the CYP2E1 gene in fetal liver.