Hori_2010_Xenobiotica_40_119

Carboxylesterase 1A1 (CES1A1) efficiently catalyses the hydrolysis of a substrate containing ester, amide, or thioester bonds. It is expressed at a high level in the human liver, but at a low level in the human kidney. In this study, we found the cause of this tissue-specific expression of the CES1A1 gene using 5-aza-2'-deoxycytidine (5-aza-dC) and bisulfite sequencing. Treatment of HEK293 cells, human embryonic kidney cells not expressing the CES1A1 gene, with 5-aza-dC caused dramatic expression of the CES1A1 gene. Bisulfite sequencing revealed that the region around the transcription start site (TSS) of the CES1A1 gene was almost entirely methylated in HEK293 cells, whereas the region was almost entirely unmethylated in HepG2 cells, human hepatoma cells. The hypomethylated DNA molecules for the region were observed in HEK293 cells treated with 5-aza-dC. In the genome obtained from the kidney, the region downstream of the TSS was methylated compared with that obtained from the liver. From these findings, it can be concluded that DNA methylation is involved in CES1A1 gene expression and that the difference between CES1A1 gene expression in the human kidney and that in the human liver may arise from the difference in DNA methylation levels in the region around the TSS.