Author:
Stern Josh Lewis,Theodorescu Dan,Vogelstein Bert,Papadopoulos Nickolas,Cech Thomas R.
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.
Funder
National Health and Medical Research Council of Australia
National Institutes of Health
The Virginia and D.K. Ludwig Fund for Cancer Research
Lustgarten Foundation for Pancreatic Cancer Research
The Sol Goldman Center for Pancreatic Cancer Research
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
160 articles.
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