Mutation of the TERT promoter, switch to active chromatin, and monoallelic TERT expression in multiple cancers

Josh Lewis Stern, Dan Theodorescu, Bert Vogelstein, Nickolas Papadopoulos, Thomas R. Cech

Research output: Contribution to journalArticlepeer-review

Abstract

Somatic mutations in the promoter of the gene for telomerase reverse transcriptase (TERT) are the most common noncoding mutations in cancer. They are thought to activate telomerase, contributing to proliferative immortality, but the molecular events driving TERT activation are largely unknown. We observed in multiple cancer cell lines that mutant TERT promoters exhibit the H3K4me2/3 mark of active chromatin and recruit the GABPA/B1 transcription factor, while the wild-type allele retains the H3K27me3 mark of epigenetic silencing; only the mutant promoters are transcriptionally active. These results suggest how a single-base-pair mutation can cause a dramatic epigenetic switch and monoallelic expression.

Original languageEnglish (US)
Pages (from-to)2219-2224
Number of pages6
JournalGenes and Development
Volume29
Issue number21
DOIs
StatePublished - Nov 1 2015

Keywords

  • Chromatin
  • Monoallelic
  • Noncoding mutations
  • Promoter
  • TERT
  • Telomerase

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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