Human telomerase reverse transcriptase (hTERT) promoter G-quadruplex DNA (hTERT promoter G4)

The Human telomerase reverse transcriptase (hTERT) promoter G-quadruplex DNA is a non-canonical secondary structure formed within the guanine-rich regulatory region of the hTERT gene (NIH, 2024). In approximately 90% of human cancers, hTERT is overexpressed, enabling telomere maintenance and cellular immortality (PubMed, 2022). The formation and stabilization of G-quadruplexes (G4s) in the hTERT promoter act as a natural transcriptional repressor by hindering the binding of essential transcription factors like Sp1 and blocking RNA polymerase progression (ACS, 2024). Consequently, small molecules that selectively bind and stabilize these G4 structures are being developed as potent anticancer agents to silence hTERT expression (ResearchGate, 2024). However, achieving high selectivity for the hTERT G4 over other genomic G4 structures remains a significant therapeutic challenge, as off-target effects could lead to unintended genomic instability (BioRxiv, 2024).

Other names

hTERT G4TERT promoter G-quadruplexhTERT core promoter G-quadruplexhTERT G-quadruplex DNA

Stabilization of the G-quadruplex structure within the hTERT promoter region, which physically blocks the binding of transcription factors (such as Sp1) and inhibits the recruitment of the transcriptional machinery, leading to the downregulation of hTERT gene expression and subsequent reduction in telomerase activity (NIH, 2024; PubMed, 2022).