Zinc Finger Protein 618 Regulates the Function of UHRF2 (Ubiquitin-like with PHD and Ring Finger Domains 2) as a Specific 5-Hydroxymethylcytosine Reader
Zinc Finger Protein 618 Regulates the Function of UHRF2 (Ubiquitin-like with PHD and Ring Finger Domains 2) as a Specific 5-Hydroxymethylcytosine Reader
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锌指蛋白 618 作为特异性 5-羟甲基胞嘧啶读取器调节 UHRF2（具有 PHD 和环指结构域 2 的类泛素）的功能。
DOI：
10.1074/jbc.m116.717314
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发表时间：
2016-06-24
影响因子：
4.8
通讯作者：
Yu, Xiaochun
中科院分区：
文献类型：
--
作者：
Liu, Yidan;Zhang, Bin;Yu, Xiaochun
5-羟甲基胞嘧啶（5 hmC）是由10 - 11易位（泰特）蛋白介导的5-甲基胞嘧啶（5 mC）氧化产生的表观遗传修饰。5 hmC与转录调控相关，并且在包括黑素瘤在内的许多癌症中降低。越来越多的证据表明，5 hmC在功能上不同于5 mC。Ubiquitin-like with PHD and ring finger domains 2（UHRF 2）是第一个已知的特异性5 hmC阅读器，其对5 hmC的亲和力高于5 mC，表明UHRF 2可能介导5 hmC的功能。结构分析已经揭示了UHRF 2 - 5 hmC体外结合的分子机制，但尚不清楚UHRF 2在体内如何识别5 hmC。在这项研究中，我们已经确定了锌图蛋白618（ZNF 618）作为一种新的结合伴侣的UHRF 2。ZNF 618特异性地与UHRF 2相互作用，但不与其parsors UHRF 1相互作用。重要的是，ZNF 618与UHRF 2共定位于富集5 hmC的基因组位点。ZNF 618的染色质定位与其与UHRF 2的相互作用无关，并且是通过其前两个锌指。相反，ZNF 618调节UHRF 2染色质定位。总的来说，我们的研究表明，ZNF 618是一个关键的蛋白质，调节UHRF 2功能作为一个特定的5 hmC阅读器在体内。
5-Hydroxymethylcytosine (5hmC) is an epigenetic modification that is generated by ten-eleven translocation (TET) protein-mediated oxidation of 5-methylcytosine (5mC). 5hmC is associated with transcription regulation and is decreased in many cancers including melanoma. Accumulating evidence has suggested that 5hmC is functionally distinct from 5mC. Ubiquitin-like with PHD and ring finger domains 2 (UHRF2) is the first known specific 5hmC reader that has higher affinity to 5hmC than 5mC, suggesting that UHRF2 might mediate 5hmC's function. Structural analysis has revealed the molecular mechanism of UHRF2-5hmC binding in vitro, but it is not clear how UHRF2 recognizes 5hmC in vivo. In this study, we have identified zinc figure protein 618 (ZNF618) as a novel binding partner of UHRF2. ZNF618 specifically interacts with UHRF2 but not its paralog UHRF1. Importantly, ZNF618 co-localizes with UHRF2 at genomic loci that are enriched for 5hmC. The ZNF618 chromatin localization is independent of its interaction with UHRF2 and is through its first two zinc fingers. Instead, ZNF618 regulates UHRF2 chromatin localization. Collectively, our study suggests that ZNF618 is a key protein that regulates UHRF2 function as a specific 5hmC reader in vivo.