title: CpG islands around exon 1 in the succinyl-CoA:3-ketoacid CoA transferase (SCOT) gene are hypomethylated even in human and mouse hepatic tissues where SCOT gene expression is completely suppressed.
abstract: In ketone body metabolism, hepatocyte-specific silencing of the succinyl-CoA:3-ketoacid CoA transferase (SCOT) gene appears to be physiologically important to avoid a futile cycle in the liver, whereas the SCOT gene is expressed in extrahepatic tissues. It is not possible to explain hepatocyte-specific silencing by cis-elements in the 2.2-kb 5' flanking region. The molecular basis of this gene silencing is unknown thus far. In the present study, the methylation status of CpG islands around exon 1 in the SCOT gene was analyzed by sodium bisulfite treatment and by sequencing of genomic DNA from the HepG2, Chang liver and HeLa human cell lines, and also from mouse liver, heart and kidney cells. Most CpG dinucleotides in the CpG island of the human SCOT promoter region were not methylated in the DNA of HeLa and Chang cells, while HepG2 DNA was hypomethylated in this CpG island. CpG dinucleotides in the mouse SCOT CpG island were almost completely unmethylated in the liver DNA as well as in the heart and kidney DNA. CpG islands around the promoter region of the SCOT gene were hypomethylated in the DNA from both human HepG2 cells and mouse liver. Hence, methylation status does not contribute to hepatocyte-specific SCOT gene silencing.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan. toshi-gif@umin.net.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukao
authors.forename: Gaixiu
authors.initials: G
authors.lastname: Zhang
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsuo
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo