Epigenetic Protection of Vertebrate Lymphoid Progenitor Cells by Dnmt1

DNA methylation is a universal epigenetic mechanism involved in regulation of gene expression and genome stability. The DNA maintenance methylase DNMT1 ensures that DNA methylation patterns are faithfully transmitted to daughter cells during cell division. Because loss of DNMT1 is lethal, a pan-orga...

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Autores principales: Iwanami, Norimasa, Takeshita, Kohei, Lawir, Divine-Fondzenyuy, Suetake, Isao, Tajima, Shoji, Sikora, Katarzyna, Trancoso, Inês, ÓMeara, Connor, Siamishi, Iliana, Takahama, Yousuke, Furutani-Seiki, Makoto, Kondoh, Hisato, Yonezawa, Yasushige, Schorpp, Michael, Boehm, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322073/
https://www.ncbi.nlm.nih.gov/pubmed/32585597
http://dx.doi.org/10.1016/j.isci.2020.101260
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author Iwanami, Norimasa
Takeshita, Kohei
Lawir, Divine-Fondzenyuy
Suetake, Isao
Tajima, Shoji
Sikora, Katarzyna
Trancoso, Inês
ÓMeara, Connor
Siamishi, Iliana
Takahama, Yousuke
Furutani-Seiki, Makoto
Kondoh, Hisato
Yonezawa, Yasushige
Schorpp, Michael
Boehm, Thomas
author_facet Iwanami, Norimasa
Takeshita, Kohei
Lawir, Divine-Fondzenyuy
Suetake, Isao
Tajima, Shoji
Sikora, Katarzyna
Trancoso, Inês
ÓMeara, Connor
Siamishi, Iliana
Takahama, Yousuke
Furutani-Seiki, Makoto
Kondoh, Hisato
Yonezawa, Yasushige
Schorpp, Michael
Boehm, Thomas
author_sort Iwanami, Norimasa
collection PubMed
description DNA methylation is a universal epigenetic mechanism involved in regulation of gene expression and genome stability. The DNA maintenance methylase DNMT1 ensures that DNA methylation patterns are faithfully transmitted to daughter cells during cell division. Because loss of DNMT1 is lethal, a pan-organismic analysis of DNMT1 function is lacking. We identified new recessive dnmt1 alleles in medaka and zebrafish and, guided by the structures of mutant proteins, generated a recessive variant of mouse Dnmt1. Each of the three missense mutations studied here distorts the catalytic pocket and reduces enzymatic activity. Because all three DNMT1 mutant animals are viable, it was possible to examine their phenotypes throughout life. The consequences of genome-wide hypomethylation of DNA of somatic tissues in the Dnmt1 mutants are surprisingly mild but consistently affect the development of the lymphoid lineage. Our findings indicate that developing lymphocytes in vertebrates are sensitive to perturbations of DNA maintenance methylation.
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spelling pubmed-73220732020-06-30 Epigenetic Protection of Vertebrate Lymphoid Progenitor Cells by Dnmt1 Iwanami, Norimasa Takeshita, Kohei Lawir, Divine-Fondzenyuy Suetake, Isao Tajima, Shoji Sikora, Katarzyna Trancoso, Inês ÓMeara, Connor Siamishi, Iliana Takahama, Yousuke Furutani-Seiki, Makoto Kondoh, Hisato Yonezawa, Yasushige Schorpp, Michael Boehm, Thomas iScience Article DNA methylation is a universal epigenetic mechanism involved in regulation of gene expression and genome stability. The DNA maintenance methylase DNMT1 ensures that DNA methylation patterns are faithfully transmitted to daughter cells during cell division. Because loss of DNMT1 is lethal, a pan-organismic analysis of DNMT1 function is lacking. We identified new recessive dnmt1 alleles in medaka and zebrafish and, guided by the structures of mutant proteins, generated a recessive variant of mouse Dnmt1. Each of the three missense mutations studied here distorts the catalytic pocket and reduces enzymatic activity. Because all three DNMT1 mutant animals are viable, it was possible to examine their phenotypes throughout life. The consequences of genome-wide hypomethylation of DNA of somatic tissues in the Dnmt1 mutants are surprisingly mild but consistently affect the development of the lymphoid lineage. Our findings indicate that developing lymphocytes in vertebrates are sensitive to perturbations of DNA maintenance methylation. Elsevier 2020-06-10 /pmc/articles/PMC7322073/ /pubmed/32585597 http://dx.doi.org/10.1016/j.isci.2020.101260 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Iwanami, Norimasa
Takeshita, Kohei
Lawir, Divine-Fondzenyuy
Suetake, Isao
Tajima, Shoji
Sikora, Katarzyna
Trancoso, Inês
ÓMeara, Connor
Siamishi, Iliana
Takahama, Yousuke
Furutani-Seiki, Makoto
Kondoh, Hisato
Yonezawa, Yasushige
Schorpp, Michael
Boehm, Thomas
Epigenetic Protection of Vertebrate Lymphoid Progenitor Cells by Dnmt1
title Epigenetic Protection of Vertebrate Lymphoid Progenitor Cells by Dnmt1
title_full Epigenetic Protection of Vertebrate Lymphoid Progenitor Cells by Dnmt1
title_fullStr Epigenetic Protection of Vertebrate Lymphoid Progenitor Cells by Dnmt1
title_full_unstemmed Epigenetic Protection of Vertebrate Lymphoid Progenitor Cells by Dnmt1
title_short Epigenetic Protection of Vertebrate Lymphoid Progenitor Cells by Dnmt1
title_sort epigenetic protection of vertebrate lymphoid progenitor cells by dnmt1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322073/
https://www.ncbi.nlm.nih.gov/pubmed/32585597
http://dx.doi.org/10.1016/j.isci.2020.101260
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