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  Epigenetic Protection of Vertebrate Lymphoid Progenitor Cells by Dnmt1

Iwanami, N., Takeshita, K., Lawir, D.-F., Suetake, I., Tajima, S., Sikora, K., et al. (2020). Epigenetic Protection of Vertebrate Lymphoid Progenitor Cells by Dnmt1. iScience, 23: 101260. doi:10.1016/j.isci.2020.101260.

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Norimasa 2 et al. 2020.pdf (Publisher version), 17MB
 
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2020
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Iwanami, Norimasa1, Author           
Takeshita, Kohei2, Author
Lawir, Divine-Fondzenyuy1, Author
Suetake, Isao2, Author
Tajima, Shoji2, Author
Sikora, Katarzyna1, Author
Trancoso, Ines1, Author           
O'Meara, Connor1, Author
Siamishi, Iliana1, Author
Takahama, Yousuke2, Author
Furutani-Seiki, Makoto2, Author
Kondoh, Hisato2, Author
Yonezawa, Yasushige2, Author
Schorpp, Michael1, Author           
Boehm, Thomas1, Author           
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1Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243647              
2External Organizations, ou_persistent22              

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Free keywords: Molecular Genetics; Phenotyping; Transcriptomics
 Abstract: 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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Language(s): eng - English
 Dates: 2020-07-24
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.isci.2020.101260
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Title: iScience
Source Genre: Journal
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Publ. Info: Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis : Elsevier
Pages: - Volume / Issue: 23 Sequence Number: 101260 Start / End Page: - Identifier: ISSN: 2589-0042
CoNE: https://pure.mpg.de/cone/journals/resource/2589-0042