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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Elsevier
2020
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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. |
format | Online Article Text |
id | pubmed-7322073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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