UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures
UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures
复制标题
UHRF2 调节局部 5-甲基胞嘧啶并抑制自发性癫痫发作
DOI：
10.1080/15592294.2017.1314423
复制
发表时间：
2017-01-01
期刊：
影响因子：
3.7
通讯作者：
Yu, Xiaochun
中科院分区：
文献类型：
--
作者：
Liu, Yidan;Zhang, Bin;Yu, Xiaochun
摘要5-甲基胞嘧啶（5 mC）修饰调节多种细胞过程，并在DNA复制后忠实地维持。除了DNA甲基转移酶（DNMT）家族蛋白外，泛素样PHD和含环指结构域蛋白1（UHRF 1）在维持5 mC水平中起重要作用。UHRF 1的缺失消除了细胞中的5 mC，并导致小鼠胚胎死亡。有趣的是，UHRF 1有一个类似的结构域和序列的蛋白质，即UHRF 2，但其生物学功能尚不清楚。在这里，我们已经产生了Uhrf 2基因敲除小鼠和UHRF 2在体内的作用的特点。uhrf 2基因敲除小鼠存活，但成年小鼠出现频繁的自发性癫痫发作和脑电活动异常。尽管没有整体DNA甲基化变化，但Uhrf 2敲除小鼠大脑中某些基因组位点的5 mC水平降低。因此，我们的研究揭示了UHRF 2在维持脑中局部5 mC水平方面的独特作用，这与其parsatile UHRF 1不同。
ABSTRACT The 5-methylcytosine (5mC) modification regulates multiple cellular processes and is faithfully maintained following DNA replication. In addition to DNA methyltransferase (DNMT) family proteins, ubiquitin-like PHD and ring finger domain-containing protein 1 (UHRF1) plays an important role in the maintenance of 5mC levels. Loss of UHRF1 abolishes 5mC in cells and leads to embryonic lethality in mice. Interestingly, UHRF1 has a paralog, UHRF2, that has similar sequence and domain architecture, but its biologic function is not clear. Here, we have generated Uhrf2 knockout mice and characterized the role of UHRF2 in vivo. Uhrf2 knockout mice are viable, but the adult mice develop frequent spontaneous seizures and display abnormal electrical activities in brain. Despite no global DNA methylation changes, 5mC levels are decreased at certain genomic loci in the brains of Uhrf2 knockout mice. Therefore, our study has revealed a unique role of UHRF2 in the maintenance of local 5mC levels in brain that is distinct from that of its paralog UHRF1.