Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/80073
Title: Depletion of sirtuin 1 (SIRT1) leads to epigenetic modifications of telomerase (TERT) gene in hepatocellular carcinoma cells
Authors: Zhang, B
Chen, J
Cheng, ASL
Ko, BCB 
Issue Date: 2014
Publisher: Public Library of Science
Source: PLoS one, 2014, v. 9, no. 1, e84931, p. 1-7 How to cite?
Journal: PLoS one 
Abstract: 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.
URI: http://hdl.handle.net/10397/80073
EISSN: 1932-6203
DOI: 10.1371/journal.pone.0084931
Rights: © 2014 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The following publication Zhang, B., Chen, J., Cheng, A. S. L., & Ko, B. C. B. (2014). Depletion of sirtuin 1 (SIRT1) leads to epigenetic modifications of telomerase (TERT) gene in hepatocellular carcinoma cells. PLoS ONE, 9(1), e84931, 1-7 is available at https://dx.doi.org/10.1371/journal.pone.0084931
Appears in Collections:Journal/Magazine Article

Access
View full-text via PolyU eLinks SFX Query
Show full item record

SCOPUSTM   
Citations

24
Last Week
0
Last month
Citations as of Jan 6, 2019

WEB OF SCIENCETM
Citations

13
Citations as of Jan 14, 2019

Page view(s)

2
Citations as of Jan 14, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.