Exploring the epigenetic regulation of telomerase reverse transcriptase (TERT) in human cancer cell lines.

Exploring the epigenetic regulation of telomerase reverse transcriptase (TERT) in human cancer cell lines.
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DOI:
10.1002/1878-0261.12798
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发表时间:
2020-10
期刊:
影响因子:
6.6
通讯作者:
Umbricht CB
Umbricht CB
中科院分区:
医学2区
文献类型:
--
作者:
McKelvey BA;Zeiger MA;Umbricht CB

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癌症中的等位基因TERT启动子甲基化和转录情况:1)双等位基因wt; 2)单等位基因突变体; 3)单等位基因wt; 4)扩增突变体。描绘了具有等位基因特异性转录水平的转录起始位点(成角度的箭头)以及近端(浅蓝色)和远端(深蓝色)TERT启动子区。未甲基化的胞嘧啶-鸟嘌呤二核苷酸(CpG)为绿色;甲基化的CpG为红色。C或T表示C->T TERT启动子突变位点。评论:https://doi.org/10.1002/1878 - 0261.12786 端粒酶调控,包括TERT启动子甲基化,一直是癌症生物学家的长期兴趣。Rowland等人现在已经极大地扩展了他们正在进行的癌细胞中TERT启动子甲基化的表征,分析了来自23种人类癌症的833种细胞系的甲基化模式。他们记录了近端启动子周围高度保守的低甲基化模式,以及更上游的高甲基化的更异质区域,两者都与癌细胞中的活性TERT表达相关。他们进一步描述了激活TERT启动子突变和等位基因甲基化和转录模式之间的相互作用。这个有价值的数据集代表了迄今为止癌细胞中最广泛的TERT启动子甲基化特征,并将有助于指导端粒酶转录调控的未来研究。评论:https://doi.org/10.1002/1878 - 0261.12786
Allelic TERT promoter methylation and transcription scenarios in cancer: 1) biallelic wt; 2) monoallelic mutant; 3) monoallelic wt; 4) amplified mutant. The transcriptional start site (angled arrow) and proximal (light blue) and distal (dark blue) TERT promoter regions with allele‐specific transcription levels are depicted. Unmethylated cytosine‐guanine dinucleotide (CpG) is green; methylated CpG is red. C or T indicates a C‐>T TERT promoter mutation site. Comment on: https://doi.org/10.1002/1878‐0261.12786 Telomerase regulation, including TERT promoter methylation, has been of long‐standing interest to cancer biologists. Rowland et al. have now vastly expanded their ongoing characterization of TERT promoter methylation in cancer cells, analyzing the methylation patterns of 833 cell lines from 23 human cancers. They document a highly conserved pattern of hypomethylation around the proximal promoter, as well as a more heterogeneous region of hypermethylation further upstream, both associated with active TERT expression in cancer cells. They further describe the interplay between activating TERT promoter mutations and allelic methylation and transcription patterns. This valuable dataset represents the most extensive characterization of TERT promoter methylation in cancer cells to date and will help guide the future study of transcriptional regulation of telomerase. Comment on: https://doi.org/10.1002/1878‐0261.12786
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