Journal
MOLECULAR ONCOLOGY
Volume 14, Issue 10, Pages 2358-2374Publisher
WILEY
DOI: 10.1002/1878-0261.12786
Keywords
epigenetics; monoallelic gene expression; promoter CpG methylation; telomerase reverse transcriptase; TERT
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Funding
- National Institutes of Health Grant [R01 GM099705]
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Telomerase reverse transcriptase (TERT) is pathologically expressed in the vast majority of human cancers, but the epigenetic regulation of its expression is only beginning to be understood. In particular, the activeTERTgene in cancer cells has been characterized as having a hypermethylated CpG island, opposite to the general association of DNA methylation with gene repression. Here, we analyzedTERTpromoter CpG methylation in 833 human cancer cell lines representing 23 different tissue types and found hypermethylation of the upstream portion of the CpG island and more conserved hypomethylation of a region including the proximalTERTpromoter and exon 1. In cell lines with monoallelic expression ofTERT, we found allelic methylation of the proximalTERTpromoter. This included cell lines with the -124 or -146 activating promoter mutation as well as wild-typeTERTcancer lines. In these cell line types, decreased proximal promoter methylation is associated with the active allele. Compared to cells with monoallelic expression ofTERT, lines with biallelic expression ofTERThad even lower methylation in the proximalTERTpromoter. Thus, in cell lines from cancers of many different tissues, theTERTproximal promoter has canonical DNA methylation, with low methylation correlating with increasedTERTexpression.
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