Universität zu Köln

Iwanami, Norimasa, Lawir, Divine-Fondzenyuy, Sikora, Katarzyna, O'Meara, Connor, Takeshita, Kohei, Schorpp, Michael and Boehm, Thomas (2020). Transgenerational inheritance of impaired larval T cell development in zebrafish. Nat. Commun., 11 (1). BERLIN: NATURE RESEARCH. ISSN 2041-1723

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Iwanami, Norimasa UNSPECIFIED UNSPECIFIED UNSPECIFIED Lawir, Divine-Fondzenyuy UNSPECIFIED UNSPECIFIED UNSPECIFIED Sikora, Katarzyna UNSPECIFIED UNSPECIFIED UNSPECIFIED O'Meara, Connor UNSPECIFIED UNSPECIFIED UNSPECIFIED Takeshita, Kohei UNSPECIFIED UNSPECIFIED UNSPECIFIED Schorpp, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Boehm, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-319450
DOI:	10.1038/s41467-020-18289-9
Journal or Publication Title:	Nat. Commun.
Volume:	11
Number:	1
Date:	2020
Publisher:	NATURE RESEARCH
Place of Publication:	BERLIN
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA METHYLTRANSFERASE GENE; METHYLATION; MOUSE; DEMETHYLATION; DYNAMICS; LYMPHOPOIESIS; THYMOPOIESIS; GENOME; DNMT1 Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31945