Transgenerational inheritance of impaired larval T cell development in zebrafish.
Alleles
Animals
Animals, Genetically Modified
Cell Differentiation
/ genetics
Core Binding Factor Alpha 3 Subunit
/ genetics
DNA (Cytosine-5-)-Methyltransferase 1
/ genetics
DNA Methylation
Epigenesis, Genetic
Female
Genes, Recessive
Genetics
Larva
/ cytology
Lymphopoiesis
/ genetics
Male
Mutation
Regulatory-Associated Protein of mTOR
/ genetics
Spermatozoa
/ metabolism
T-Lymphocytes
/ physiology
Zebrafish
/ genetics
Zebrafish Proteins
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 09 2020
09 09 2020
Historique:
received:
28
10
2019
accepted:
11
08
2020
entrez:
10
9
2020
pubmed:
11
9
2020
medline:
2
10
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32908148
doi: 10.1038/s41467-020-18289-9
pii: 10.1038/s41467-020-18289-9
pmc: PMC7481223
doi:
Substances chimiques
Core Binding Factor Alpha 3 Subunit
0
Regulatory-Associated Protein of mTOR
0
Zebrafish Proteins
0
runx3 protein, zebrafish
0
DNA (Cytosine-5-)-Methyltransferase 1
EC 2.1.1.37
Dnmt1 protein, zebrafish
EC 2.1.1.37
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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