The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
hTERT Is Expressed in Cancer Cell Lines Despite Promoter DNA Methylation by Preservation of Unmethylated DNA and Active Chromatin around the Transcription Start Site
Published version of a preprint
Abstract
hTERT, which encodes the catalytic subunit of telomerase and is expressed in most immortalized and cancer cells, has been reported to have increased DNA methylation in its promoter region in many cancers. This pattern is inconsistent with observations that DNA methylation of promoter CpG islands is typically associated with gene silencing. Here, we provide a comprehensive analysis of promoter DNA methylation, chromatin patterns, and expression of hTERT in cancer and immortalized cells. Methylation-specific PCR and bisulfite sequencing of the hTERT promoter in breast, lung, and colon cancer cells show that all cancer cell lines retain alleles with little or no methylation around the transcription start site despite being densely methylated in a region 600 bp upstream of the transcription start site. By real-time reverse transcription-PCR, all cancer cell lines express hTERT. Chromatin immunoprecipitation (ChIP) analysis reveals that both active (acetyl-H3K9 and dimethyl-H3K4) and inactive (trimethyl-H3K9 and trimethyl-H3K27) chromatin marks are present across the hTERT promoter. However, using a novel approach combining methylation analysis of ChIP DNA, we show that active chromatin marks are associated with unmethylated DNA, whereas inactive marks of chromatin are associated with methylated DNA in the region around the transcription start site. These results show that DNA methylation patterns of the hTERT promoter (−150 to +150 around the transcription start) are consistent with the usual dynamics of gene expression in that the absence of methylation in this region and the association with active chromatin marks allow for the continued expression of hTERT. [Cancer Res 2007;67(1):194–201]
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“These data suggest that the absence of methylation and the association with active chromatin marks around the transcription start site allow for the expression of hTERT (Fig. 1), indicating that the DNA methylation pattern of the hTERT promoter is consistent with the usual dynamics of gene expression.”
From Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [62]
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Cites
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Self-citationRole of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing
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Gene Silencing in Cancer in Association with Promoter Hypermethylation
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Self-citationIdentification of a specific telomere terminal transferase activity in tetrahymena extracts
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The RNA Component of Human Telomerase
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Self-citationIncidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma
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Anwar, I., Pandith, A. A., Rasool, S. U. A., Manzoor, U., Iqbal, M. K., Lone, I. M., Walvir, N. M., Lone, T. A., & Wani, M. S. (2025) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2025.11.017
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Samy, M. (2010) · theses.fr (ABES) · doi:10.70675/07050b7dz1056z4e65za6f1z34cea95a398b
Régulation épigénétique de la télomérase dans un modèle de leucémie aiguë promyélocytaire
Garsuault, D. (2019) · theses.fr (ABES) · doi:10.70675/b7ec8d0fz1565z4bfdz8f5ezad2c36aaffea
Chebly, A., & Chevret, E. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1893675
Escape from replicative crisis and immortalization precedes complex genome evolutionPreprint
Schmidt, T. T., Cosenza, M. R., Popay, T. M., Przetocka, S., Haggblom, C., Allsing, N., Lande, K., Grimstead, J. W., Williams, A. E., Baird, D. A., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.09.758087
Hasan, R. (2010) · Brunel University Research Archive (BURA) (Brunel University London)
Metadata
- Authors
- Zinn, R. L., Pruitt, K., Eguchi, S., Baylin, S. B., & Herman, J. G.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Cancer Research
- Published
- 2007-01-01
- Volume
- 67
- Issue
- 1
- Pages
- 194-201
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2069698023
- Cited by
- 210
- References
- 28
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 11 · 2022: 9 · 2021: 6 · 2020: 13 · 2019: 15 · 2018: 11 · 2017: 9 · 2016: 16 · 2015: 15 · 2014: 11 · 2013: 9 · 2012: 12
- FWCI
- 6.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA088843, P50CA088843)
- National Institute of Environmental Health Sciences (R01ES011858, ES 11858)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Keywords
- hTERT, telomerase reverse transcriptase, promoter methylation, transcription start sites, gene expression, cancer cell lines, CpG islands, histone modifications, H3K9 acetylation, H3K4 dimethylation, H3K9 trimethylation, H3K27me3, gene silencing, breast cancer, lung cancer, colon cancer
- MeSH terms
- Alleles, Breast Neoplasms, Chromatin, Colonic Neoplasms, Humans, Leukemia, Lung Neoplasms, Neoplasms, Promoter Regions, Genetic, Gene Expression, Caco-2 Cells, Telomerase, DNA Methylation, Transcription Initiation Site, HCT116 Cells, Cell Line, Tumor
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