Format

Send to

Choose Destination
Genes Dev. 2015 Nov 1;29(21):2219-24. doi: 10.1101/gad.269498.115. Epub 2015 Oct 29.

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

Author information

1
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA; Howard Hughes Medical Institute, University of Colorado BioFrontiers Institute, Boulder, Colorado 80309, USA;
2
University of Colorado Comprehensive Cancer Center, Aurora, Colorado 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, USA; Department of Surgery (Urology), University of Colorado, Aurora, Colorado 80045, USA;
3
Ludwig Center, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA; Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland 21231, USA.
4
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA; Howard Hughes Medical Institute, University of Colorado BioFrontiers Institute, Boulder, Colorado 80309, USA; University of Colorado Comprehensive Cancer Center, Aurora, Colorado 80045, USA;

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.

KEYWORDS:

TERT; chromatin; monoallelic; noncoding mutations; promoter; telomerase

PMID:
26515115
PMCID:
PMC4647555
DOI:
10.1101/gad.269498.115
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center