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Molecular structure, evolution and mechanism of genomic imprinting

基因组印记的分子结构、进化及机制

基本信息

批准号：
16590232
负责人：
MUKAI Tsunehiro
金额：
$ 2.3万
依托单位：
Saga University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590232/
关键词：
Imprinting Imprinting center DNA methylation Murr1 U2af1-rs1

项目摘要

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.

人MURR 1基因是小鼠Murr 1基因的同源基因，该基因在成年人脑中以母系等位基因为主，在第一内含子中含有另一个印迹基因U2 af 12-rs 1。发现人MURR 1不具有U2 af 1-rs 1直系同源物，并且在组织（包括成人脑）中双等位基因表达。三个基因，确定周围的Murr 1和他们的直系同源物周围MURR 1的双等位基因表达。这些结果表明，小鼠印迹位点是有限的，在小鼠中的U2 af 1-rs 1的引入导致该位点的印迹在一个小的区域。U2 af 1-rs 1的CpG岛（CGI）是这些基因座中发现的唯一甲基化差异区域。对生殖细胞中U2 af 1-rs 1 CGI的详细甲基化分析导致鉴定出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Murr 1/U2 af 1-rs 1基因座的印迹控制区。小鼠U2 af 1-rs 1基因在胚胎早期的甲基化状态检测显示，在母体中甲基化。用原代成纤维细胞检测组蛋白修饰状态。使用各种组蛋白抗体（针对H3 Ac、H4 Ac、H3 mK 4）进行芯片测定，并显示父系是有活性的。