PDF(Pubmed)
Abstract：
The tripartite motif-containing protein 66 (TRIM66, also known as TIF1-delta) is a PHD-Bromo-containing protein primarily expressed in post-meiotic male germ cells known as spermatids. Biophysical assays showed that the TRIM66 PHD-Bromodomain binds to H3 N-terminus only when lysine 4 is unmethylated. We addressed TRIM66\'s role in reproduction by loss-of-function genetics in the mouse. Males homozygous for Trim66-null mutations produced functional spermatozoa. Round spermatids lacking TRIM66 up-regulated a network of genes involved in histone acetylation and H3K4 methylation. Profiling of H3K4me3 patterns in the sperm produced by the Trim66-null mutant showed minor alterations below statistical significance. Unexpectedly, Trim66-null males, but not females, sired pups overweight at birth, hence revealing that Trim66 mutations cause a paternal effect phenotype.
摘要：
含三方基序的蛋白66(TRIM66,也称为TIF1-delta)是主要在称为精子细胞的减数分裂后雄性生殖细胞中表达的含PHD-溴的蛋白。生物物理试验表明，只有当赖氨酸4未甲基化时，TRIM66PHD-溴结构域才与H3N末端结合。我们通过小鼠功能丧失遗传学研究了TRIM66在生殖中的作用。Trim66无效突变纯合的雄性产生功能性精子。缺乏TRIM66的圆形精子细胞上调了参与组蛋白乙酰化和H3K4甲基化的基因网络。Trim66-null突变体产生的精子中H3K4me3模式的分析显示出低于统计显著性的微小变化。出乎意料的是,Trim66-null雄性，但不是女性，母猪出生时超重，因此揭示Trim66突变引起父系效应表型。
