Human telomerase reverse transcriptase regulation by DNA methylation, transcription factor binding and alternative splicing (Review)

  • Authors:
    • Brittany A. Avin
    • Christopher B. Umbricht
    • Martha A. Zeiger
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  • Published online on: October 20, 2016     https://doi.org/10.3892/ijo.2016.3743
  • Pages: 2199-2205
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Abstract

The catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), plays an essential role in telomere maintenance to oppose cellular senescence and, is highly regulated in normal and cancerous cells. Regulation of hTERT occurs through multiple avenues, including a unique pattern of CpG promoter methylation and alternative splicing. Promoter methylation affects the binding of transcription factors, resulting in changes in expression of the gene. In addition to expression level changes, changes in promoter binding can affect alternative splicing in a cotranscriptional manner. The alternative splicing of hTERT results in either the full length transcript which can form the active telomerase complex with hTR, or numerous inactive isoforms. Both regulation strategies are exploited in cancer to activate telomerase, however, the exact mechanism is unknown. Therefore, unraveling the link between promoter methylation status and alternative splicing for hTERT could expose yet another level of hTERT regulation. In an attempt to provide insight into the cellular control of active telomerase in cancer, this review will discuss our current perspective on CpG methylation of the hTERT promoter region, summarize the different forms of alternatively spliced variants, and examine examples of transcription factor binding that affects splicing.
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December-2016
Volume 49 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Avin BA, Umbricht CB and Zeiger MA: Human telomerase reverse transcriptase regulation by DNA methylation, transcription factor binding and alternative splicing (Review). Int J Oncol 49: 2199-2205, 2016
APA
Avin, B.A., Umbricht, C.B., & Zeiger, M.A. (2016). Human telomerase reverse transcriptase regulation by DNA methylation, transcription factor binding and alternative splicing (Review). International Journal of Oncology, 49, 2199-2205. https://doi.org/10.3892/ijo.2016.3743
MLA
Avin, B. A., Umbricht, C. B., Zeiger, M. A."Human telomerase reverse transcriptase regulation by DNA methylation, transcription factor binding and alternative splicing (Review)". International Journal of Oncology 49.6 (2016): 2199-2205.
Chicago
Avin, B. A., Umbricht, C. B., Zeiger, M. A."Human telomerase reverse transcriptase regulation by DNA methylation, transcription factor binding and alternative splicing (Review)". International Journal of Oncology 49, no. 6 (2016): 2199-2205. https://doi.org/10.3892/ijo.2016.3743