Molecular structure, evolution and mechanism of genomic imprinting

人类MURR1是小鼠MURR1基因的同源基因，先前报道仅在成人大脑中印迹，母体等位基因显性表达，并且在第一个内含子中包含另一个印迹基因U2af12-rs1。人类MURR1被发现不含U2af1-rs1同源基因，并在包括成人大脑在内的组织中双等位表达。在Murr1周围鉴定的3个基因及其在Murr1周围的同源基因呈双等位表达。这些发现表明小鼠印迹位点局限于一个小区域，U2af1-rs1在小鼠体内的引入引起了该位点的印迹。U2af1-rs1位点的CpG岛（CGI）与母体甲基化是这些位点中唯一发现的差异甲基化区域。对生殖细胞中的U2af1-rs1 CGI进行了详细的甲基化分析，鉴定出一个具有卵母细胞特异性甲基化的区域。这些结果表明该区域是小鼠Murr1/U2af1-rs1基因座的印迹控制区。在胚胎早期检测小鼠U2af1-rs1的甲基化状态，结果显示母性甲基化。用原代成纤维细胞检测组蛋白修饰状态。Chip实验使用多种组蛋白抗体（抗H3Ac， H4Ac, H3mK4）进行，显示父系具有活性。

Human MURR1 is an orthologue of mouse Murr1 gene, which was previously reported to be imprinted only in adult brain with a maternal allele-predominant expression and to contain another imprinted gene, U2af12-rs1, in the first intron. Human MURR1 was found not to harbor the U2af1-rs1 orthologue and to be expressed biallelically in tissues, including adult brain. Three genes, identified around Murr1 and their orthologues around MURR1 were expressed biallelically. These findings suggest that the mouse imprinting locus is limited to a small region and the introduction of U2af1-rs1 in mouse causes the imprinting of this locus. The CpG island(CGI) at U2af1-rs1 with maternal methylation was the only differentially methylated region among CGIs found in these loci. Detailed methylation analyses of the U2af1-rs1 CGI in germ cells led to identification of a region with oocyte-specific methylation. These results suggest that this region is the imprinting control region of the Murr1/U2af1-rs1 locus in mouse. The methylation status of mouse U2af1-rs1 was examined during early stage of embryo and showed to be methylated maternally. The status of histone modification was examined using primary fibroblast cell. The Chip assay was performed using various histone antibodies (against H3Ac, H4Ac, H3mK4) and showed paternally to be active.