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Polymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene

Tao Xu, De Cheng, Yuanjun Zhao, Jinglong Zhang, Xiaolu Zhu, Fan Zhang, Gang Chen, Yang Wang, Xiufeng Yan, Gavin P. Robertson, Shobhan Gaddameedhi, Philip J. Lazarus, Shuwen Wang, Jiyue Zhu

Proceedings of the National Academy of Sciences · 2021 · ▲ 11 citations

Telomere attrition Cellular senescence Telomerase activation Human

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Abstract

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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Provenance

Source: OpenAlex
DOI: 10.1073/pnas.2019043118
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Fetched: 2026-10-10 MST

Cite this

APA

Xu, T., Cheng, D., Zhao, Y., Zhang, J., Zhu, X., Zhang, F., Chen, G., Wang, Y., Yan, X., Robertson, G.P., Gaddameedhi, S., Lazarus, P.J., Wang, S., & Zhu, J. (2021). Polymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene. <em>Proceedings of the National Academy of Sciences</em>. https://doi.org/10.1073/pnas.2019043118

Vancouver

Xu T, Cheng D, Zhao Y, Zhang J, Zhu X, Zhang F, et al. Polymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene. Proceedings of the National Academy of Sciences. 2021. doi:10.1073/pnas.2019043118.

BibTeX

@unpublished{tao2021Polymo, title = {Polymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene}, author = {Tao Xu and De Cheng and Yuanjun Zhao and Jinglong Zhang and Xiaolu Zhu and Fan Zhang and Gang Chen and Yang Wang and Xiufeng Yan and Gavin P. Robertson and Shobhan Gaddameedhi and Philip J. Lazarus and Shuwen Wang and Jiyue Zhu}, journal = {Proceedings of the National Academy of Sciences}, year = {2021}, doi = {10.1073/pnas.2019043118}, }