TERT Promoter Mutations Enhance Telomerase Activation by Long-Range Chromatin Interactions.
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.
Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, Texas.
Jaewon
J
Min
Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, Texas. jerry.shay@utsouthwestern.edu.
Jerry W
JW
Shay
D064113:CRISPR-Cas Systems; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5; D051268:GA-Binding Protein Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
D002843:Chromatin; D051268:GA-Binding Protein Transcription Factor; C495661:GABPA protein, human; C509186:TERT protein, human; D019098:Telomerase