Hypomethylation of ERVs in the sperm of mice haploinsufficient for the histone methyltransferase Setdb1 correlates with a paternal effect on phenotype.
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.
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.
Lucia
L
Daxinger
Department of Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086 Australia.
Harald
H
Oey
Department of Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086 Australia.
Luke
L
Isbel
Epigenetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Brisbane 4006, QLD, Australia.
Nadia C
NC
Whitelaw
Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney 2052, Australia.
Neil A
NA
Youngson
Department of Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3086 Australia.
Alex
A
Spurling
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
Kelly K D
KK
Vonk
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.
Emma
E
Whitelaw
D000818:Animals; D019175:DNA Methylation; D020077:Endogenous Retroviruses / Q000235:genetics*; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D057895:Haploinsufficiency; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D008297:Male; D051379:Mice; D000072740:Paternal Inheritance; D010641:Phenotype; D040641:Quantitative Trait Loci; D018626:Retroelements; D013094:Spermatozoa / Q000737:chemistry; D000073336:Whole Genome Sequencing
D018626:Retroelements; D011495:Histone-Lysine N-Methyltransferase; C516239:SETDB1 protein, mouse