ArticleMolecular biology of the cell2010
Distinct and temporal roles of nucleosomal remodeling and histone deacetylation in the repression of the hTERT gene.
Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Acute exercise leads to regulation of telomere-associated genes and microRNA expression in immune cells.PloS one · 2014Trial
- Article
- Exploring hTERT promoter methylation in cutaneous T-cell lymphomas.Molecular oncology · 2022Article
- ETS variant transcription factor 5 and c-Myc cooperate in derepressing the human telomerase gene promoter via composite ETS/E-box motifs.The Journal of biological chemistry · 2020Article
- Repression of telomerase gene promoter requires human-specific genomic context and is mediated by multiple HDAC1-containing corepressor complexes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Article
- Telomerase Regulation from Beginning to the End.Genes · 2016Review
- Review
- Review
- Human Telomerase Reverse Transcriptase (hTERT) Transcription Requires Sp1/Sp3 Binding to the Promoter and a Permissive Chromatin Environment.The Journal of biological chemistry · 2015Article
- Single cell measurement of telomerase expression and splicing using microfluidic emulsion cultures.Nucleic acids research · 2015Article
- Significance of epigenetic landscape in cartilage regeneration from the cartilage development and pathology perspective.Stem cells and development · 2014Review
- Epigenetic regulation of the human telomerase reverse transciptase gene: A potential therapeutic target for the treatment of leukemia (Review).Oncology letters · 2013Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
hTERT, the human telomerase reverse transcriptase, is highly expressed in stem cells and embryonic tissues but undetectable in most adult somatic cells. To understand its repression mechanisms in somatic cells, we investigated the endogenous hTERT gene regulation during differentiation of human leukemic HL60 cells. Our study revealed that silencing of the hTERT promoter was a biphasic process. Within 24 h after initiation of differentiation, hTERT mRNA expression decreased dramatically, accompanied by increased expression of Mad1 gene and disappearance of a nucleosome-free region at the hTERT core promoter. Subsequent to this early repression, nucleosomal remodeling continued at the promoter and downstream region for several days, as demonstrated by micrococcal nuclease and restriction enzyme accessibility assays. This later nucleosomal remodeling correlated with stable silencing of the hTERT promoter. Progressive changes of core histone modifications occurred throughout the entire differentiation process. Surprisingly, inhibition of histone deacetylation at the hTERT promoter did not prevent hTERT repression or nucleosomal deposition, indicating that nucleosomal deposition at the core promoter, but not histone deacetylation, was the cause of transcriptional repression. Our data also suggested that succeeding nucleosomal remodeling and histone deacetylation worked in parallel to establish the stable repressive status of hTERT gene in human somatic cells.
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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.