TERT Promoter Mutations Enhance Telomerase Activation by Long-Range Chromatin Interactions

Abstract

Although single-nucleotide somatic mutations in the proximal promoter of the human telomerase reverse transcriptase (TERT) gene create novel consensus sequences for transcription factors that enhance TERT expression, the precise mechanism of how telomerase is reactivated in cancer cells remains poorly understood. In this issue, Akıncılar and colleagues identify a potential mechanism of TERT reactivation that is mediated by a novel long-range chromatin interaction between the TERT promoter on chromosome 5p and a 300-kb upstream region. This permits recruitment of the transcription factor GABPA in mutant TERT promoters but not in wild-type promoters. Cancer Discov; 6(11); 1212-4. ©2016 AACRSee related article by Akıncılar and colleagues, p. 1276.

Figure 1

TERT promoter mutation reactivates the silenced TERT promoter via generating long-range chromatin interactions. Ak1nc1lar and colleagues (1) show that TERT reactivation by the proximal promoter mutation is directly mediated by a novel long-range chromatin interaction between the TERT promoter and a 300 kb upstream region (chr5: 1,556,087-1,558,758). GABPA proteins might generate long-range chromatin interactions by linking the mutant TERT promoter and the specific interacting region.