학술논문
Hypomethylation of ERVs in the sperm of mice haploinsufficient for the histone methyltransferase Setdb1 correlates with a paternal effect on phenotype.
Document Type
Academic Journal
Author
Daxinger L; Department of Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086 Australia.; Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.; Oey H; Department of Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086 Australia.; Isbel L; Department of Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086 Australia.; Whitelaw NC; Epigenetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Brisbane 4006, QLD, Australia.; Youngson NA; Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney 2052, Australia.; Spurling A; Department of Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086 Australia.; Vonk KK; Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.; Whitelaw E; Department of Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086 Australia.; Epigenetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Brisbane 4006, QLD, Australia.
Source
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
Subject
Language
English
Abstract
The number of reports of paternal epigenetic influences on the phenotype of offspring in rodents is increasing but the molecular events involved remain unclear. Here, we show that haploinsufficiency for the histone 3 lysine 9 methyltransferase Setdb1 in the sire can influence the coat colour phenotype of wild type offspring. This effect occurs when the allele that directly drives coat colour is inherited from the dam, inferring that the effect involves an "in trans" step. The implication of this finding is that epigenetic state of the sperm can alter the expression of genes inherited on the maternally derived chromosomes. Whole genome bisulphite sequencing revealed that Setdb1 mutant mice show DNA hypomethylation at specific classes of transposable elements in the sperm. Our results identify Setdb1 as a paternal effect gene in the mouse and suggest that epigenetic inheritance may be more likely in individuals with altered levels of epigenetic modifiers.