Iwanami, Norimasa, Takeshita, Kohei, Lawir, Divine-Fondzenyuy, Suetake, Isao ORCID: 0000-0002-1246-8474, Tajima, Shoji, Sikora, Katarzyna, Trancoso, Ines ORCID: 0000-0003-0214-4684, OMeara, Connor, Siamishi, Iliana, Takahama, Yousuke ORCID: 0000-0002-4992-9174, Furutani-Seiki, Makoto, Kondoh, Hisato, Yonezawa, Yasushige, Schorpp, Michael and Boehm, Thomas (2020). Epigenetic Protection of Vertebrate Lymphoid Progenitor Cells by Dnmt1. iScience, 23 (7). CAMBRIDGE: CELL PRESS. ISSN 2589-0042

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Iwanami, NorimasaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Takeshita, KoheiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lawir, Divine-FondzenyuyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suetake, IsaoUNSPECIFIEDorcid.org/0000-0002-1246-8474UNSPECIFIED
Tajima, ShojiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sikora, KatarzynaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trancoso, InesUNSPECIFIEDorcid.org/0000-0003-0214-4684UNSPECIFIED
OMeara, ConnorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siamishi, IlianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Takahama, YousukeUNSPECIFIEDorcid.org/0000-0002-4992-9174UNSPECIFIED
Furutani-Seiki, MakotoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kondoh, HisatoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yonezawa, YasushigeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schorpp, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boehm, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-325745
DOI: 10.1016/j.isci.2020.101260
Journal or Publication Title: iScience
Volume: 23
Number: 7
Date: 2020
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2589-0042
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DNA METHYLTRANSFERASE 1; C-FOS; DEFINITIVE HEMATOPOIESIS; THYMUS DEVELOPMENT; CRYSTAL-STRUCTURE; GENETIC-EVIDENCE; METHYLATION; MOUSE; MUTATIONS; DYNAMICSMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32574

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