Open AccessPolymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene
Author(s) -
Tao Xu,
De Cheng,
Yuanjun Zhao,
Jinglong Zhang,
Xiaolu Zhu,
Fan Zhang,
Gang Chen,
Yang Wang,
Xiufeng Yan,
Gavin P. Robertson,
Shobhan Gaddameedhi,
Philip Lazarus,
Shuwen Wang,
Jiyue Zhu
Publication year - 2021
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2019043118
Subject(s) - telomerase reverse transcriptase , biology , telomere , telomerase , enhancer , genetics , transcription (linguistics) , gene , promoter , transcription factor , microbiology and biotechnology , gene expression , linguistics , philosophy
Significance Repetitive DNA sequences are abundant in the human genome, and their high variabilities contribute to genetic diversity and disease susceptibility. Here, we report that an intronic variable number tandem repeat element, VNTR2-1, is critical for the transcription of the human telomerase reverse transcriptase (hTERT ) gene in a cell-context–dependent manner. Removal of this element at its native genomic site in cancer cells resulted in telomere shortening, cellular senescence, and impaired tumor growth. VNTR2-1 length, consisting of 53 to 160 copies of 42-bp repeats, varies widely in human populations. hTERT alleles with short VNTR2-1 are underrepresented in African American centenarians, suggesting that hTERT regulation by VNTR2-1 plays a role in human aging and tumorigenesis.
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