ArticleThe Journal of biological chemistry2010
Grainyhead-like 2 enhances the human telomerase reverse transcriptase gene expression by inhibiting DNA methylation at the 5'-CpG island in normal human keratinocytes.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 70 citations in OpenAlex.
- Identification of copper related biomarkers in breast cancer using machine learning.Discover oncology · 2025Article
- GRHL2 regulates keratinocyte EMT-MET dynamics and scar formation during cutaneous wound healing.Cell death & disease · 2024Article
- The evolving genetic landscape of telomere biology disorder dyskeratosis congenita.EMBO molecular medicine · 2024Article
- Grainyhead-like-2, an epithelial master programmer, promotes interferon induction and suppresses breast cancer recurrence.Molecular immunology · 2024Article
- hPSC-derived sacral neural crest enables rescue in a severe model of Hirschsprung's disease.Cell stem cell · 2023Article
- GRHL2 Regulation of Growth/Motility Balance in Luminal versus Basal Breast Cancer.International journal of molecular sciences · 2023Article
- GRHL2-controlled gene expression networks in luminal breast cancer.Cell communication and signaling : CCS · 2023Article
- Grainyhead-like 2 is required for morphological integrity of mouse embryonic stem cells and orderly formation of inner ear-like organoids.Frontiers in cell and developmental biology · 2023Article
- FKBP52 and FKBP51 differentially regulate the stability of estrogen receptor in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Matrix stiffness epigenetically regulates the oncogenic activation of the Yes-associated protein in gastric cancer.Nature biomedical engineering · 2021Article
- Matrix stiffness epigenetically regulates the oncogenic activation of the Yes-associated protein in gastric cancer.Nature biomedical engineering · 2021Article
- Grainyhead-like 2 as a double-edged sword in development and cancer.American journal of translational research · 2020Review
- Spotlight on the Granules (Grainyhead-Like Proteins) - From an Evolutionary Conserved Controller of Epithelial Trait to Pioneering the Chromatin Landscape.Frontiers in molecular biosciences · 2020Review
- The role of GRHL2 and epigenetic remodeling in epithelial-mesenchymal plasticity in ovarian cancer cells.Communications biology · 2019Article
- Human Papillomavirus 16 E6 Induces FoxM1B in Oral Keratinocytes through GRHL2.Journal of dental research · 2018Article
- hTERT peptide fragment GV1001 demonstrates radioprotective and antifibrotic effects through suppression of TGF‑β signaling.International journal of molecular medicine · 2018Article
- Grainyhead-like 2 (GRHL2) knockout abolishes oral cancer development through reciprocal regulation of the MAP kinase and TGF-β signaling pathways.Oncogenesis · 2018Article
- Article
- Roles of Grainyhead-like transcription factors in cancer.Oncogene · 2017Review
- Grhl2 reduces invasion and migration through inhibition of TGFβ-induced EMT in gastric cancer.Oncogenesis · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We recently identified Grainyhead-like 2 (GRHL2) as a novel transcription factor that binds to and regulates the activity of the human telomerase reverse transcriptase (hTERT) gene promoter. In this study, we investigated the biological functions of GRHL2 and the molecular mechanism underlying hTERT gene regulation by GRHL2. Retroviral transduction of GRHL2 in normal human keratinocytes (NHK) led to a significant extension of replicative life span, whereas GRHL2 knockdown notably repressed telomerase activity and cell proliferation. Using promoter magnetic precipitation coupled with Western blotting, we confirmed the binding of GRHL2 to the hTERT promoter and mapped the minimal binding region at -53 to -13 of the promoter. Furthermore, mutation analysis revealed the three nucleotides from -21 to -19 to be critical for GRHL2 binding. Because hTERT expression is regulated in part by DNA methylation, we determined the effects of GRHL2 on the methylation status of the hTERT promoter. Senescent NHK exhibited hypermethylation of the CpG island, which occurred with the loss of hTERT expression. On the contrary, the promoter remained hypomethylated in GRHL2-transduced NHK, irrespective of cell proliferation status. Also, knockdown of endogenous GRHL2 led to hypermethylation of the promoter. These results indicate that GRHL2 regulates the hTERT expression through an epigenetic mechanism and controls the cellular life span.
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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.