Cell Cycle-Dependent Turnover of 5-Hydroxymethyl Cytosine in Mouse Embryonic Stem Cells

Hydroxymethylcytosine in the genome is reported to be an intermediate of demethylation. In the present study, we demonstrated that maintenance methyltransferase Dnmt1 scarcely catalyzed hemi-hydroxymethylated DNA and that the hemi-hydroxymethylated DNA was not selectively recognized by the SRA domai...

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Autores principales: Otani, Junji, Kimura, Hironobu, Sharif, Jafar, Endo, Takaho A., Mishima, Yuichi, Kawakami, Toru, Koseki, Haruhiko, Shirakawa, Masahiro, Suetake, Isao, Tajima, Shoji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858372/
https://www.ncbi.nlm.nih.gov/pubmed/24340069
http://dx.doi.org/10.1371/journal.pone.0082961
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author Otani, Junji
Kimura, Hironobu
Sharif, Jafar
Endo, Takaho A.
Mishima, Yuichi
Kawakami, Toru
Koseki, Haruhiko
Shirakawa, Masahiro
Suetake, Isao
Tajima, Shoji
author_facet Otani, Junji
Kimura, Hironobu
Sharif, Jafar
Endo, Takaho A.
Mishima, Yuichi
Kawakami, Toru
Koseki, Haruhiko
Shirakawa, Masahiro
Suetake, Isao
Tajima, Shoji
author_sort Otani, Junji
collection PubMed
description Hydroxymethylcytosine in the genome is reported to be an intermediate of demethylation. In the present study, we demonstrated that maintenance methyltransferase Dnmt1 scarcely catalyzed hemi-hydroxymethylated DNA and that the hemi-hydroxymethylated DNA was not selectively recognized by the SRA domain of Uhrf1, indicating that hydroxymethylcytosine is diluted in a replication-dependent manner. A high level of 5-hydroxymethylcytosine in mouse embryonic stem cells was produced from the methylcytosine supplied mainly by de novo-type DNA methyltransferases Dnmt3a and Dnmt3b. The promoter regions of the HoxA gene cluster showed a high hydroxymethylation level whilst the methylcytosine level was quite low, suggesting that methylated CpG is actively hydroxylated during proliferation. All the results indicate that removal and production of hydroxymethylcytosine are regulated in replication-dependent manners in mouse embryonic stem cells.
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spelling pubmed-38583722013-12-11 Cell Cycle-Dependent Turnover of 5-Hydroxymethyl Cytosine in Mouse Embryonic Stem Cells Otani, Junji Kimura, Hironobu Sharif, Jafar Endo, Takaho A. Mishima, Yuichi Kawakami, Toru Koseki, Haruhiko Shirakawa, Masahiro Suetake, Isao Tajima, Shoji PLoS One Research Article Hydroxymethylcytosine in the genome is reported to be an intermediate of demethylation. In the present study, we demonstrated that maintenance methyltransferase Dnmt1 scarcely catalyzed hemi-hydroxymethylated DNA and that the hemi-hydroxymethylated DNA was not selectively recognized by the SRA domain of Uhrf1, indicating that hydroxymethylcytosine is diluted in a replication-dependent manner. A high level of 5-hydroxymethylcytosine in mouse embryonic stem cells was produced from the methylcytosine supplied mainly by de novo-type DNA methyltransferases Dnmt3a and Dnmt3b. The promoter regions of the HoxA gene cluster showed a high hydroxymethylation level whilst the methylcytosine level was quite low, suggesting that methylated CpG is actively hydroxylated during proliferation. All the results indicate that removal and production of hydroxymethylcytosine are regulated in replication-dependent manners in mouse embryonic stem cells. Public Library of Science 2013-12-10 /pmc/articles/PMC3858372/ /pubmed/24340069 http://dx.doi.org/10.1371/journal.pone.0082961 Text en © 2013 Otani 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
Otani, Junji
Kimura, Hironobu
Sharif, Jafar
Endo, Takaho A.
Mishima, Yuichi
Kawakami, Toru
Koseki, Haruhiko
Shirakawa, Masahiro
Suetake, Isao
Tajima, Shoji
Cell Cycle-Dependent Turnover of 5-Hydroxymethyl Cytosine in Mouse Embryonic Stem Cells
title Cell Cycle-Dependent Turnover of 5-Hydroxymethyl Cytosine in Mouse Embryonic Stem Cells
title_full Cell Cycle-Dependent Turnover of 5-Hydroxymethyl Cytosine in Mouse Embryonic Stem Cells
title_fullStr Cell Cycle-Dependent Turnover of 5-Hydroxymethyl Cytosine in Mouse Embryonic Stem Cells
title_full_unstemmed Cell Cycle-Dependent Turnover of 5-Hydroxymethyl Cytosine in Mouse Embryonic Stem Cells
title_short Cell Cycle-Dependent Turnover of 5-Hydroxymethyl Cytosine in Mouse Embryonic Stem Cells
title_sort cell cycle-dependent turnover of 5-hydroxymethyl cytosine in mouse embryonic stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858372/
https://www.ncbi.nlm.nih.gov/pubmed/24340069
http://dx.doi.org/10.1371/journal.pone.0082961
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