Methylation of CpG islands in the rat 7-dehydrocholesterol reductase promoter suppresses transcriptional activation.
In mammals, 7-dehydrocholesterol reductase (Dhcr7) is the terminal enzyme in cholesterol biosynthesis. We previously reported that the Dhcr7 proximal promoter (-179 to +1), which contains CpG islands, is responsible for sterol-mediated expression of the rat gene. In the present study, we examined whether methylation of this region affects the transcriptional activity of the Dhcr7 gene. In vitro DNA methylation of the Dhcr7 promoter and luciferase-reporter assays showed that DNA methylation of the CpG islands suppressed transcription. Furthermore, treatment of the methylated Dhcr7 promoter with the demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-CdR), reversed the suppression of promoter activity. These results indicate that methylation of the CpG islands is an important transcriptional regulatory mechanism in the Dhcr7 promoter.
Kim
Jai-Hyun
JH
Department of Biological Sciences and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
Hwang
Eun-Ha
EH
Park
Hye-Jung
HJ
Paik
Young-Ki
YK
Shim
Yhong-Hee
YH
D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D000077209:Decitabine; D015971:Gene Expression Regulation, Enzymologic; D020868:Gene Silencing; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D000077209:Decitabine; D008156:Luciferases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase; D001374:Azacitidine