UHRF1 plays a role in maintaining DNA methylation in mammalian cells
UHRF1 plays a role in maintaining DNA methylation in mammalian cells
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DOI：
10.1126/science.1147939
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发表时间：
2007-09-21
期刊：
影响因子：
56.9
通讯作者：
Jacobsen, Steven E.
中科院分区：
文献类型：
--
作者：
Bostick, Magnolia;Kim, Jong Kyong;Jacobsen, Steven E.
哺乳动物的表观遗传部分依赖于DNA甲基化模式在整个发育过程中的稳健传播。我们发现，蛋白质UHRF 1（泛素样，含有PHD和RING指结构域1），也被称为NP95在小鼠和ICBP 90在人类，是维持DNA甲基化所必需的。UHRF 1在整个S期与维持DNA甲基转移酶蛋白DNMT 1共定位。UHRF 1似乎通过与DNMT 1的直接相互作用将DNMT 1拴系到染色质上。此外，UHRF 1含有甲基DNA结合结构域，SRA（SET和RING相关）结构域，其显示出与半甲基化CG位点（DNMT 1的生理底物）的强优先结合。这些数据表明，UHRF 1可能有助于招募DNMT 1半甲基化DNA，以促进DNA甲基化的忠实维持。
Epigenetic inheritance in mammals relies in part on robust propagation of DNA methylation patterns throughout development. We show that the protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1), also known as NP95 in mouse and ICBP90 in human, is required for maintaining DNA methylation. UHRF1 colocalizes with the maintenance DNA methyltransferase protein DNMT1 throughout S phase. UHRF1 appears to tether DNMT1 to chromatin through its direct interaction with DNMT1. Furthermore UHRF1 contains a methyl DNA binding domain, the SRA (SET and RING associated) domain, that shows strong preferential binding to hemimethylated CG sites, the physiological substrate for DNMT1. These data suggest that UHRF1 may help recruit DNMT1 to hemimethylated DNA to facilitate faithful maintenance of DNA methylation.