Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Aug 18;7(8):50.
doi: 10.3390/genes7080050.

Transcription Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene

Muhammad Khairul Ramlee  1 , Jing Wang  2 , Wei Xun Toh  3 , Shang Li  4   5
Affiliations
Review

Transcription Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene

Muhammad Khairul Ramlee et al. Genes (Basel). .

Abstract

Embryonic stem cells and induced pluripotent stem cells have the ability to maintain their telomere length via expression of an enzymatic complex called telomerase. Similarly, more than 85%-90% of cancer cells are found to upregulate the expression of telomerase, conferring them with the potential to proliferate indefinitely. Telomerase Reverse Transcriptase (TERT), the catalytic subunit of telomerase holoenzyme, is the rate-limiting factor in reconstituting telomerase activity in vivo. To date, the expression and function of the human Telomerase Reverse Transcriptase (hTERT) gene are known to be regulated at various molecular levels (including genetic, mRNA, protein and subcellular localization) by a number of diverse factors. Among these means of regulation, transcription modulation is the most important, as evident in its tight regulation in cancer cell survival as well as pluripotent stem cell maintenance and differentiation. Here, we discuss how hTERT gene transcription is regulated, mainly focusing on the contribution of trans-acting factors such as transcription factors and epigenetic modifiers, as well as genetic alterations in hTERT proximal promoter.

Keywords: mutation; promoter; telomerase; telomere; transcription regulation.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic of transcription factor binding sites in human Telomerase Reverse Transcriptase (hTERT) promoter. Chromosomal sequence extending from 3.5 kb upstream and 150 bp downstream of hTERT translation start site (+1) is represented by the gray box. Horizontal lines above and below the box indicate approximate binding sites of respective transcription factors. Blue lines: hotspot promoter mutations (“-124” corresponds to C228T mutation; “-146” corresponds to C250T mutation); green: activator; red: repressor; purple: regulator with dual roles; dotted line: regulator bound to sites created by hotspot mutations.
Figure 2
Figure 2
Frequency of human telomerase reverse transcriptase (hTERT) promoter mutations in various cancer types. (a) Overall hTERT promoter mutation frequencies of various cancer types plotted in descending order; (b) Overall hTERT promoter mutation frequencies of various cancer types with breakdown of individual frequencies of C228T, C250T, and all other mutations. The overall mutation frequencies of hTERT promoter were compiled from all relevant publications on human cancer genome sequencing. The label “n” corresponds to the total number of tumors sequenced among different studies for the same tumor type. Error bars correspond to the standard errors in mutation frequencies calculated among different studies on the same tumor type. Only studies with at least 20 samples sequenced were included in this study. Only studies which provided the detailed breakdown of different mutation sites were included in (b). Refer to Table 3 for the list of references used to compile this figure.
Figure 2
Figure 2
Frequency of human telomerase reverse transcriptase (hTERT) promoter mutations in various cancer types. (a) Overall hTERT promoter mutation frequencies of various cancer types plotted in descending order; (b) Overall hTERT promoter mutation frequencies of various cancer types with breakdown of individual frequencies of C228T, C250T, and all other mutations. The overall mutation frequencies of hTERT promoter were compiled from all relevant publications on human cancer genome sequencing. The label “n” corresponds to the total number of tumors sequenced among different studies for the same tumor type. Error bars correspond to the standard errors in mutation frequencies calculated among different studies on the same tumor type. Only studies with at least 20 samples sequenced were included in this study. Only studies which provided the detailed breakdown of different mutation sites were included in (b). Refer to Table 3 for the list of references used to compile this figure.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Blackburn E.H. Telomere states and cell fates. Nature. 2000;408:53–56. doi: 10.1038/35040500. - DOI - PubMed
    1. De Lange T. How shelterin solves the telomere end-protection problem. Cold Spring Harb. Symp. Quant. Biol. 2010;75:167–177. doi: 10.1101/sqb.2010.75.017. - DOI - PubMed
    1. Makarov V.L., Hirose Y., Langmore J.P. Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell. 1997;88:657–666. doi: 10.1016/S0092-8674(00)81908-X. - DOI - PubMed
    1. Wright W.E., Tesmer V.M., Huffman K.E., Levene S.D., Shay J.W. Normal human chromosomes have long G-rich telomeric overhangs at one end. Genes Dev. 1997;11:2801–2809. doi: 10.1101/gad.11.21.2801. - DOI - PMC - PubMed
    1. Feng J., Funk W.D., Wang S.S., Weinrich S.L., Avilion A.A., Chiu C.P., Adams R.R., Chang E., Allsopp R.C., Yu J., et al. The RNA component of human telomerase. Science. 1995;269:1236–1241. doi: 10.1126/science.7544491. - DOI - PubMed