Template activating factor-I epigenetically regulates the TERT transcription in human cancer cells

Abstract Telomere, the terminus of linear chromosome in eukaryotes, is composed of specific repeat DNA which is mainly synthesized by a protein complex called telomerase. The maintenance of telomere DNA is important for unlimited proliferative capacity of cancer cells. The telomerase activity is con...

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Autores principales: Kohsuke Kato, Atsushi Kawaguchi, Kyosuke Nagata
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/7d5e3641ed684d32bda976d4bba12503
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spelling oai:doaj.org-article:7d5e3641ed684d32bda976d4bba125032021-12-02T17:19:15ZTemplate activating factor-I epigenetically regulates the TERT transcription in human cancer cells10.1038/s41598-021-97009-92045-2322https://doaj.org/article/7d5e3641ed684d32bda976d4bba125032021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97009-9https://doaj.org/toc/2045-2322Abstract Telomere, the terminus of linear chromosome in eukaryotes, is composed of specific repeat DNA which is mainly synthesized by a protein complex called telomerase. The maintenance of telomere DNA is important for unlimited proliferative capacity of cancer cells. The telomerase activity is controlled by the expression level of telomerase reverse transcriptase (TERT), a catalytic unit of telomerase, in some species including human. Therefore, to reveal the regulatory mechanisms of the transcription of TERT gene is important for understanding the tumor development. We found that template activating factor-I (TAF-I), a multifunctional nuclear protein, is involved in the transcriptional activation of TERT for the maintenance of telomere DNA in HeLa cells. TAF-I maintains the histone H3 modifications involved in transcriptional activation and hypomethylated cytosines in CpG dinucleotides around the transcription start site (TSS) in the TERT gene locus. Collectively, TAF-I is involved in the maintenance of telomere DNA through the regulation of TERT transcription, then consequently the occurrence and/or recurrence of cancer cells.Kohsuke KatoAtsushi KawaguchiKyosuke NagataNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kohsuke Kato
Atsushi Kawaguchi
Kyosuke Nagata
Template activating factor-I epigenetically regulates the TERT transcription in human cancer cells
description Abstract Telomere, the terminus of linear chromosome in eukaryotes, is composed of specific repeat DNA which is mainly synthesized by a protein complex called telomerase. The maintenance of telomere DNA is important for unlimited proliferative capacity of cancer cells. The telomerase activity is controlled by the expression level of telomerase reverse transcriptase (TERT), a catalytic unit of telomerase, in some species including human. Therefore, to reveal the regulatory mechanisms of the transcription of TERT gene is important for understanding the tumor development. We found that template activating factor-I (TAF-I), a multifunctional nuclear protein, is involved in the transcriptional activation of TERT for the maintenance of telomere DNA in HeLa cells. TAF-I maintains the histone H3 modifications involved in transcriptional activation and hypomethylated cytosines in CpG dinucleotides around the transcription start site (TSS) in the TERT gene locus. Collectively, TAF-I is involved in the maintenance of telomere DNA through the regulation of TERT transcription, then consequently the occurrence and/or recurrence of cancer cells.
format article
author Kohsuke Kato
Atsushi Kawaguchi
Kyosuke Nagata
author_facet Kohsuke Kato
Atsushi Kawaguchi
Kyosuke Nagata
author_sort Kohsuke Kato
title Template activating factor-I epigenetically regulates the TERT transcription in human cancer cells
title_short Template activating factor-I epigenetically regulates the TERT transcription in human cancer cells
title_full Template activating factor-I epigenetically regulates the TERT transcription in human cancer cells
title_fullStr Template activating factor-I epigenetically regulates the TERT transcription in human cancer cells
title_full_unstemmed Template activating factor-I epigenetically regulates the TERT transcription in human cancer cells
title_sort template activating factor-i epigenetically regulates the tert transcription in human cancer cells
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/7d5e3641ed684d32bda976d4bba12503
work_keys_str_mv AT kohsukekato templateactivatingfactoriepigeneticallyregulatestheterttranscriptioninhumancancercells
AT atsushikawaguchi templateactivatingfactoriepigeneticallyregulatestheterttranscriptioninhumancancercells
AT kyosukenagata templateactivatingfactoriepigeneticallyregulatestheterttranscriptioninhumancancercells
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