Transgenerational inheritance of impaired larval T cell development in zebrafish

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.

Global Host Responses to the Microbiota at Single Cell Resolution in Gnotobiotic Zebrafish

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Paternal transgenerational nutritional epigenetic effect: A new insight into nutritional manipulation to reduce the use of antibiotics in animal feeding

“…However, zebrafish inherit the paternal DNA methylome configuration ( Jiang et al., 2013 ; Potok et al., 2013 ) ( Table 1 ). Recent studies demonstrated the absence of global DNA methylation erasure in the zebrafish germline and extensive amplification and demethylation of the oocyte-specific fem-rDNA cluster during gonad transformation, which suggested the retention of paternal epigenetic memory in the developing zebrafish germline ( Iwanami et al., 2020 ; Skvortsova et al., 2019 ). These studies have proved the existence of paternal transgenerational epigenetics in non-mammalian (anamniote) vertebrates.…”

Small RNAs and chromatin in the multigenerational epigenetic landscape ofCaenorhabditis elegans

“…True TEI has been clearly demonstrated in numerous animal models, from C. elegans to fish to mice [3,9,90,98,99], but most of this evidence is from artificial, laboratory-based conditions. How does this translate into the natural environmental context?…”