Transcriptional repression by the proximal exonic region at the human TERT gene (original) (raw)
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TERT Promoter Mutations Increase Sense and Antisense Transcription from the TERT Promoter
Biomedicines, 2021
Background: Chief among mechanisms of telomerase reverse transcriptase (TERT) reactivation is the appearance of mutations in the TERT promoter. The two main TERT promoter mutations are C>T transitions located −146C>T and −124C>T upstream from the translational start site. They generate a novel Ets/TCF binding site. Both mutations are mutually exclusive and −124C>T is strikingly overrepresented in most cancers. We investigated whether this mutational bias and mutual exclusion could be due to transcriptional constraints. Methods: We compared sense and antisense transcription of a panel of TERT promoter-luciferase vectors harboring the −124C>T and -146C>T mutations alone or together. lncRNA TAPAS levels were measured by RT-PCR. Results: Both mutations generally increased TERT transcription by 2–4-fold regardless of upstream and downstream regulatory elements. The double mutant increased transcription in an additive fashion, arguing against a direct transcriptional con...
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