ArticleProceedings of the National Academy of Sciences of the United States of America2005
Differential cis-regulation of human versus mouse TERT gene expression in vivo: identification of a human-specific repressive element.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Positioning TERT at the apex of aging.Nature aging · 2026Review
- Gut microbial metabolite butyrate boosts p53-expressing telomerase-specific oncolytic adenovirus efficacy by enhancing infectivity and activating MHC-I/cGAS-STING.Cancer immunology, immunotherapy : CII · 2025Article
- The transcription complex p52-ETS1 is essential for germinal center formation.Nature immunology · 2025Article
- Effect of aging and exercise on hTERT expression in thymus tissue of hTERT transgenic bacterial artificial chromosome mice.GeroScience · 2025Article
- Telomere function and regulation from mouse models to human ageing and disease.Nature reviews. Molecular cell biology · 2025Review
- Telomerase reverse transcriptase gene knock-in unleashes enhanced longevity and accelerated damage repair in mice.Aging cell · 2025Article
- Modification of the telomerase gene with human regulatory sequences resets mouse telomeres to human length.Nature communications · 2025Article
- Establishment and Characterization of a Chicken Myoblast Cell Line.International journal of molecular sciences · 2024Article
- Humanization of the mouseResearch square · 2024Article
- Review
- Acute Exercise Regulates hTERT Gene Expression and Alternative Splicing in the hTERT-BAC Transgenic Mouse Model.Medicine and science in sports and exercise · 2022Article
- TAZ maintains telomere length in TNBC cells by mediating Rad51C expression.Breast cancer research : BCR · 2021Article
- Polymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- A Pan-Cancer Study of Somatic TERT Promoter Mutations and Amplification in 30,773 Tumors Profiled by Clinical Genomic Sequencing.The Journal of molecular diagnostics : JMD · 2021Article
- Review
- Engineering a humanized telomerase reverse transcriptase gene in mouse embryonic stem cells.Scientific reports · 2019Article
- DNA Hypermethylation Downregulates Telomerase Reverse Transcriptase (TERT) duringJournal of oncology · 2019Article
- The Emerging Roles for Telomerase in the Central Nervous System.Frontiers in molecular neuroscience · 2018Review
- Nanoscale Assembly of High-Mobility Group AT-Hook 2 Protein with DNA Replication Fork.Biophysical journal · 2017Article
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Authors and funding
9 authors.
Funding
Abstract
In vivo expression of human telomerase is significantly different from that of mouse telomerase. To assess the basis for this difference, a bacterial artificial chromosome clone containing the entire hTERT (human telomerase reverse transcriptase) gene was introduced in mice. In these transgenic mice, expression of the hTERT transgene was similar to that of endogenous hTERT in humans, rather than endogenous mTERT (mouse telomerase reverse transcriptase). In tissues and cells showing a striking difference in expression levels between hTERT in humans and mTERT in mice (i.e., liver, kidney, lung, uterus, and fibroblasts), expression of the hTERT transgene in transgenic mice was repressed, mimicking hTERT in humans. The transcriptional activity of the hTERT promoter was much lower than that of the mTERT promoter in mouse embryonic fibroblasts or human fibroblasts. Mutational analysis of the hTERT and mTERT promoters revealed that a nonconserved GC-box within the hTERT promoter was responsible for the human-specific repression. These results reveal that a difference in cis-regulation of transcription, rather than transacting transcription factors, is critical to species differences in tissue-specific TERT expression. Our data also suggest that the GC-box-mediated, human-specific mechanism for TERT repression is impaired in human cancers. This study represents a detailed characterization of the functional difference in a gene promoter of mice versus humans and provides not only important insight into species-specific regulation of telomerase and telomeres but also an experimental basis for generating mice humanized for telomerase enzyme and its pattern of expression.
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