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Transgenerational inheritance of impaired larval T cell development in zebrafish

Author

Listed:
  • Norimasa Iwanami

    (Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics
    Utsunomiya University)

  • Divine-Fondzenyuy Lawir

    (Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics
    University of Cologne)

  • 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)

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.

Suggested Citation

  • Norimasa Iwanami & Divine-Fondzenyuy Lawir & Katarzyna Sikora & Connor O´Meara & Kohei Takeshita & Michael Schorpp & Thomas Boehm, 2020. "Transgenerational inheritance of impaired larval T cell development in zebrafish," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18289-9
    DOI: 10.1038/s41467-020-18289-9
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    Cited by:

    1. Donna M. Bond & Oscar Ortega-Recalde & Melanie K. Laird & Takashi Hayakawa & Kyle S. Richardson & Finlay.C. B. Reese & Bruce Kyle & Brooke E. McIsaac-Williams & Bruce C. Robertson & Yolanda Heezik & A, 2023. "The admixed brushtail possum genome reveals invasion history in New Zealand and novel imprinted genes," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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