PUBLICATION

Epigenetic Protection of Vertebrate Lymphoid Progenitor Cells by Dnmt1

Authors
Iwanami, N., Takeshita, K., Lawir, D.F., Suetake, I., Tajima, S., Sikora, K., Trancoso, I., ÓMeara, C., Siamishi, I., Takahama, Y., Furutani-Seiki, M., Kondoh, H., Yonezawa, Y., Schorpp, M., Boehm, T.
ID
ZDB-PUB-200626-19
Date
2020
Source
iScience   23: 101260 (Journal)
Registered Authors
Boehm, Tom, Furutani-Seiki, Makoto, Kondoh, Hisato, Schorpp, Michael
Keywords
Molecular Genetics, Phenotyping, Transcriptomics
Datasets
GEO:GSE98648, GEO:GSE141114
MeSH Terms
none
PubMed
32585597 Full text @ iScience
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping