Transgenerational inheritance of impaired larval T cell development in zebrafish

Norimasa Iwanami, Divine-Fondzenyuy Lawir, Katarzyna Sikora, Connor O´Meara, Kohei Takeshita, Michael Schorpp and Thomas Boehm ()
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Norimasa Iwanami: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics
Divine-Fondzenyuy Lawir: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics
Katarzyna Sikora: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics
Connor O´Meara: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics
Kohei Takeshita: RIKEN SPring-8 Center, Sayo
Michael Schorpp: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics
Thomas Boehm: Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18289-9

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