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Telomerase reverse transcriptase (TERT) activation plays an important role in cancer development by enabling the immortalization of cells.TERTregulation is multifaceted, and its promoter methylation has been implicated in controlling expression through alteration in transcription factor binding. We have characterizedTERTpromoter methylation, transcription factor binding, andTERTexpression levels in five differentiated thyroid cancer (DTC) cell lines and six normal thyroid tissue samples by targeted bisulfite sequencing, ChIP‐qPCR, and qRT‐PCR. DTC cell lines express varying levels ofTERTand exhibitTERTpromoter methylation patterns similar to patterns seen in other telomerase positive cancer cell lines. The minimal promoter immediately surrounding the transcription start site is hypomethylated, while further upstream portions show dense methylation. In contrast, theTERTpromoter in normal thyroid tissue is largely unmethylated throughout and expressesTERTminimally. Transcription factor binding is also affected byTERTmutation status. The E‐twenty‐six (ETS) factor GABPA exhibitsTERTbinding in theTERTmutant DTC cells only, and allele‐specific methylation patterns at the minimal promoter were observed as well, which may indicate allele‐specific factor recruitment at the minimal promoter. Furthermore, we identified binding sites for activators MYC and GSC in the hypermethylated upstream region, pointing to its possible importance inTERTregulation. Overall,TERTexpression and telomerase activity depend on the interplay of multiple regulatory mechanisms includingTERTpromoter methylation, mutation status, and recruitment of transcription factors. This work explores of the interplay between these regulatory mechanisms and offers insight into cellular control of active telomerase in human cancer.