Unusual distribution of DNA methylation within the hTERT CpG island in tissues and cell lines.
The promoter region of the gene encoding the human telomerase reverse transcriptase (hTERT) is located in a CpG island and was shown to be regulated, at least in part, by DNA methylation. However, the observed correlation between hTERT methylation and gene expression was opposite to the general model of regulation by DNA methylation. We established a detailed mapping of methylcytosines at the CpG island (-1539 to +1732) surrounding the hTERT promoter in tissues and cell lines. In telomerase-positive samples, a methylation of all the CpG sites was observed for the hTERT promoter region (-500 to +1), whereas the exonic part (+1 to +450) revealed an unstable methylation pattern. Incomplete methylation of the proximal exon region could be necessary for, at least, a low level of hTERT transcription. In conclusion, hypermethylation of the CpG island plays a complex but essential role in the expression of hTERT in telomerase-positive cells.
Guilleret
Isabelle
I
Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, Bugnon 25, CH-1011 Lausanne, Switzerland.
Benhattar
Jean
J
D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid; D019098:Telomerase / Q000235:genetics*
D004268:DNA-Binding Proteins; D019098:Telomerase