ArticleCell reports2021
Human telomerase is directly regulated by non-telomeric TRF2-G-quadruplex interaction.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 49 citations in OpenAlex.
- Terfa Safeguards GABAergic Inhibition and Neuronal Excitability in Zebrafish Through a Foxj3-Linked Transcriptional Mechanism.Neuroscience bulletin · 2026Article
- TRF2 couples muscle stem cell identity to regenerative repair.Science advances · 2026Article
- Revealing G4 Structures as Drug Targets: Exploring the Potential of Novel Therapeutic Agents.Research (Washington, D.C.) · 2026Review
- Telomeres control human telomerase (eLife · 2025Article
- AURKB and PI3K/AKT/mTOR pathways converge to regulateiScience · 2025Article
- The immortality mechanism of TERT promoter mutant cancers is self-reinforcing and reversible.Molecular cell · 2025Article
- Unravelling Convergent Signaling Mechanisms Underlying the Aging-Disease Nexus Using Computational Language Analysis.Current issues in molecular biology · 2025Article
- Article
- A Compendium of G-Flipon Biological Functions That Have Experimental Validation.International journal of molecular sciences · 2024Review
- Article
- Structural Unfolding of G-Quadruplexes: From Small Molecules to Antisense Strategies.Molecules (Basel, Switzerland) · 2024Review
- The shelterin protein expansion of telomere dynamics: Linking early life adversity, life history, and the hallmarks of aging.Neuroscience and biobehavioral reviews · 2023Review
- Non-canonical telomere protection role of FOXO3a of human skeletal muscle cells regulated by the TRF2-redox axis.Communications biology · 2023Article
- Reactivation of telomerase reverse transcriptase expression in cancer: the role of TERT promoter mutations.Frontiers in cell and developmental biology · 2023Review
- Telomeres expand sphere of influence: emerging molecular impact of telomeres in non-telomeric functions.Trends in genetics : TIG · 2023Review
- Interaction between non-coding RNAs, mRNAs and G-quadruplexes.Cancer cell international · 2022Review
- Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Human telomerase reverse transcriptase (hTERT) remains suppressed in most normal somatic cells. Resulting erosion of telomeres leads eventually to replicative senescence. Reactivation of hTERT maintains telomeres and triggers progression of >90% of cancers. However, any direct causal link between telomeres and telomerase regulation remains unclear. Here, we show that the telomere-repeat-binding-factor 2 (TRF2) binds hTERT promoter G-quadruplexes and recruits the polycomb-repressor EZH2/PRC2 complex. This is causal for H3K27 trimethylation at the hTERT promoter and represses hTERT in cancer as well as normal cells. Two highly recurrent hTERT promoter mutations found in many cancers, including ∼83% glioblastoma multiforme, that are known to destabilize hTERT promoter G-quadruplexes, showed loss of TRF2 binding in patient-derived primary glioblastoma multiforme cells. Ligand-induced G-quadruplex stabilization restored TRF2 binding, H3K27-trimethylation, and hTERT re-suppression. These results uncover a mechanism of hTERT regulation through a telomeric factor, implicating telomere-telomerase molecular links important in neoplastic transformation, aging, and regenerative therapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.