Transgenerational inheritance of impaired larval T cell development in zebrafish
Open Access
- 9 September 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-13
- https://doi.org/10.1038/s41467-020-18289-9
Abstract
Evidence for transgenerational inheritance of epigenetic information in vertebrates is scarce. Aberrant patterns of DNA methylation in gametes may set the stage for transmission into future generations. Here, we describe a viable hypomorphic allele of dnmt1 in zebrafish that causes widespread demethylation of CpG dinucleotides in sperm and somatic tissues. We find that homozygous mutants are essentially normal, with the exception of drastically impaired lymphopoiesis, affecting both larval and adult phases of T cell development. The phenotype of impaired larval (but not adult) T cell development is transmitted to subsequent generations by genotypically wildtype fish. We further find that about 200 differentially methylated regions in sperm DNA of transmitting and non-transmitting males, including hypermethylated sites associated with runx3 and rptor genes, whose reduced activities are associated with impaired larval T cell development. Our results indicate a particular sensitivity of larval T cell development to transgenerationally inherited epimutations.Funding Information
- Max-Planck-Gesellschaft (n/a)
This publication has 60 references indexed in Scilit:
- The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ CellsMolecular Cell, 2012
- Functions of DNA methylation: islands, start sites, gene bodies and beyondNature Reviews Genetics, 2012
- Global profiling of DNA methylation erasure in mouse primordial germ cellsGenome Research, 2012
- Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1)Proceedings of the National Academy of Sciences of the United States of America, 2011
- Loss of Dnmt1 catalytic activity reveals multiple roles for DNA methylation during pancreas development and regenerationDevelopmental Biology, 2009
- Assessing the Impact of Transgenerational Epigenetic Variation on Complex TraitsPLoS Genetics, 2009
- DNA Demethylation in Zebrafish Involves the Coupling of a Deaminase, a Glycosylase, and Gadd45Cell, 2008
- Zebra Fish Dnmt1 and Suv39h1 Regulate Organ-Specific Terminal Differentiation during DevelopmentMolecular and Cellular Biology, 2006
- New member of the winged-helix protein family disrupted in mouse and rat nude mutationsNature, 1994
- Targeted mutation of the DNA methyltransferase gene results in embryonic lethalityCell, 1992