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端粒酶逆转录酶(TERT)启动子突变通过长程染色质相互作用增强端粒酶激活

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

作者信息

Min Jaewon, Shay Jerry W

机构信息

Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, Texas.

出版信息

Cancer Discov. 2016 Nov;6(11):1212-1214. doi: 10.1158/2159-8290.CD-16-1050.

DOI:10.1158/2159-8290.CD-16-1050
PMID:27807101
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5111399/
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.

摘要

尽管人类端粒酶逆转录酶(TERT)基因近端启动子中的单核苷酸体细胞突变会为增强TERT表达的转录因子创造新的共有序列,但癌细胞中端粒酶如何重新激活的精确机制仍知之甚少。在本期杂志中,阿金奇拉尔及其同事确定了一种TERT重新激活的潜在机制,该机制由5号染色体p臂上的TERT启动子与上游300 kb区域之间新型的长程染色质相互作用介导。这使得转录因子GABPA能够在突变型TERT启动子中募集,而在野生型启动子中则不能。《癌症发现》;6(11);1212 - 1214。©2016美国癌症研究协会。见阿金奇拉尔及其同事的相关文章,第1276页。

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本文引用的文献

1
Long-Range Chromatin Interactions Drive Mutant TERT Promoter Activation.长距离染色质相互作用驱动突变 TERT 启动子激活。
Cancer Discov. 2016 Nov;6(11):1276-1291. doi: 10.1158/2159-8290.CD-16-0177. Epub 2016 Sep 20.
2
Role of Telomeres and Telomerase in Aging and Cancer.端粒与端粒酶在衰老和癌症中的作用。
Cancer Discov. 2016 Jun;6(6):584-93. doi: 10.1158/2159-8290.CD-16-0062. Epub 2016 Mar 30.
3
A novel two-step genome editing strategy with CRISPR-Cas9 provides new insights into telomerase action and TERT gene expression.一种采用CRISPR-Cas9的新型两步基因组编辑策略为端粒酶作用和TERT基因表达提供了新见解。
Genome Biol. 2015 Nov 10;16:231. doi: 10.1186/s13059-015-0791-1.
4
Mutation of the TERT promoter, switch to active chromatin, and monoallelic TERT expression in multiple cancers.端粒酶逆转录酶(TERT)启动子突变、向活性染色质转变以及多种癌症中的单等位基因TERT表达
Genes Dev. 2015 Nov 1;29(21):2219-24. doi: 10.1101/gad.269498.115. Epub 2015 Oct 29.
5
Non-canonical NF-κB signalling and ETS1/2 cooperatively drive C250T mutant TERT promoter activation.非经典NF-κB信号通路与ETS1/2协同驱动C250T突变型TERT启动子激活。
Nat Cell Biol. 2015 Oct;17(10):1327-38. doi: 10.1038/ncb3240. Epub 2015 Sep 21.
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Cancer. The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer.癌症。转录因子GABP在癌症中选择性地结合并激活突变的端粒酶逆转录酶(TERT)启动子。
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