Daxinger Lucia, Oey Harald, Isbel Luke, Whitelaw Nadia C, Youngson Neil A, Spurling Alex, Vonk Kelly K D, Whitelaw Emma
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.
Sci Rep. 2016 Apr 26;6:25004. doi: 10.1038/srep25004.
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.
关于父系表观遗传对啮齿动物后代表型影响的报道数量正在增加，但其中涉及的分子事件仍不清楚。在这里，我们表明，父本中组蛋白3赖氨酸9甲基转移酶Setdb1的单倍剂量不足会影响野生型后代的毛色表型。当直接决定毛色的等位基因从母本遗传时，就会出现这种效应，这表明该效应涉及一个“反式”步骤。这一发现的意义在于，精子的表观遗传状态可以改变从母本遗传的染色体上基因的表达。全基因组亚硫酸氢盐测序显示，Setdb1突变小鼠的精子中特定类型的转座元件存在DNA低甲基化。我们的结果确定Setdb1为小鼠中的一个父系效应基因，并表明表观遗传修饰水平改变的个体中表观遗传遗传可能更易发生。
