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Depletion of Sirtuin 1 (SIRT1) Leads to Epigenetic Modifications of Telomerase (TERT) Gene in Hepatocellular Carcinoma Cells
Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that is implicated in plethora of biological processes, including metabolism, aging, stress response, and tumorigenesis. Telomerase (TERT) is essential for telomere maintenance. Activation of TERT is considered a cr...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885646/ https://www.ncbi.nlm.nih.gov/pubmed/24416313 http://dx.doi.org/10.1371/journal.pone.0084931 |
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author | Zhang, Bin Chen, Juan Cheng, Alfred S. L. Ko, Ben C. B. |
author_facet | Zhang, Bin Chen, Juan Cheng, Alfred S. L. Ko, Ben C. B. |
author_sort | Zhang, Bin |
collection | PubMed |
description | Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that is implicated in plethora of biological processes, including metabolism, aging, stress response, and tumorigenesis. Telomerase (TERT) is essential for telomere maintenance. Activation of TERT is considered a crucial step in tumorigenesis, and therefore it is a potential therapeutic target against cancer. We have recently found that SIRT1 expression is highly elevated in hepatocellular carcinoma, and the depletion of SIRT1 leads to substantial reduction in TERT mRNA and protein expression. However, the underlying molecular mechanism of SIRT1-dependent TERT expression remains uncharacterized. Here, we elucidated if SIRT1 regulates TERT expression via transcriptional, epigenetic and post-transcriptional mechanisms. We report that depletion of SIRT1 does not lead to significant change in transcriptional activity and CpG methylation patterns of the TERT promoter, nor does it affect mRNA stability or 3′-UTR regulation of TERT. Intriguingly, depletion of SIRT1 is associated with substantial induction of acetylated histone H3-K9 and reduction of trimethyl H3-K9 at the TERT gene, which are known to be associated with gene activation. Our data revealed that SIRT1 regulates histone acetylation and methylation at the TERT promoter. We postulated that SIRT1 may regulate TERT expression via long-range interaction, or via yet unidentified histone modifications. |
format | Online Article Text |
id | pubmed-3885646 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38856462014-01-10 Depletion of Sirtuin 1 (SIRT1) Leads to Epigenetic Modifications of Telomerase (TERT) Gene in Hepatocellular Carcinoma Cells Zhang, Bin Chen, Juan Cheng, Alfred S. L. Ko, Ben C. B. PLoS One Research Article Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that is implicated in plethora of biological processes, including metabolism, aging, stress response, and tumorigenesis. Telomerase (TERT) is essential for telomere maintenance. Activation of TERT is considered a crucial step in tumorigenesis, and therefore it is a potential therapeutic target against cancer. We have recently found that SIRT1 expression is highly elevated in hepatocellular carcinoma, and the depletion of SIRT1 leads to substantial reduction in TERT mRNA and protein expression. However, the underlying molecular mechanism of SIRT1-dependent TERT expression remains uncharacterized. Here, we elucidated if SIRT1 regulates TERT expression via transcriptional, epigenetic and post-transcriptional mechanisms. We report that depletion of SIRT1 does not lead to significant change in transcriptional activity and CpG methylation patterns of the TERT promoter, nor does it affect mRNA stability or 3′-UTR regulation of TERT. Intriguingly, depletion of SIRT1 is associated with substantial induction of acetylated histone H3-K9 and reduction of trimethyl H3-K9 at the TERT gene, which are known to be associated with gene activation. Our data revealed that SIRT1 regulates histone acetylation and methylation at the TERT promoter. We postulated that SIRT1 may regulate TERT expression via long-range interaction, or via yet unidentified histone modifications. Public Library of Science 2014-01-08 /pmc/articles/PMC3885646/ /pubmed/24416313 http://dx.doi.org/10.1371/journal.pone.0084931 Text en © 2014 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zhang, Bin Chen, Juan Cheng, Alfred S. L. Ko, Ben C. B. Depletion of Sirtuin 1 (SIRT1) Leads to Epigenetic Modifications of Telomerase (TERT) Gene in Hepatocellular Carcinoma Cells |
title | Depletion of Sirtuin 1 (SIRT1) Leads to Epigenetic Modifications of Telomerase (TERT) Gene in Hepatocellular Carcinoma Cells |
title_full | Depletion of Sirtuin 1 (SIRT1) Leads to Epigenetic Modifications of Telomerase (TERT) Gene in Hepatocellular Carcinoma Cells |
title_fullStr | Depletion of Sirtuin 1 (SIRT1) Leads to Epigenetic Modifications of Telomerase (TERT) Gene in Hepatocellular Carcinoma Cells |
title_full_unstemmed | Depletion of Sirtuin 1 (SIRT1) Leads to Epigenetic Modifications of Telomerase (TERT) Gene in Hepatocellular Carcinoma Cells |
title_short | Depletion of Sirtuin 1 (SIRT1) Leads to Epigenetic Modifications of Telomerase (TERT) Gene in Hepatocellular Carcinoma Cells |
title_sort | depletion of sirtuin 1 (sirt1) leads to epigenetic modifications of telomerase (tert) gene in hepatocellular carcinoma cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885646/ https://www.ncbi.nlm.nih.gov/pubmed/24416313 http://dx.doi.org/10.1371/journal.pone.0084931 |
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