Geminivirus-encoded TrAP suppressor inhibits the histone methyltransferase SUVH4/KYP to counter host defense.
Geminivirus-encoded TrAP suppressor inhibits the histone methyltransferase SUVH4/KYP to counter host defense.
复制标题
DOI：
10.7554/elife.06671
复制
发表时间：
2015-09-07
期刊：
影响因子：
7.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Castillo-González C;Liu X;Huang C;Zhao C;Ma Z;Hu T;Sun F;Zhou Y;Zhou X;Wang XJ;Zhang X
转录基因沉默（TGS）可以作为一种天然免疫，在整个真核生物中抵抗入侵的DNA病毒。双生病毒编码TrAP蛋白以抑制TGS途径。在这里，我们鉴定了拟南芥H3 K9 me 2组蛋白甲基转移酶，Su（var）3-9同源物4/Kryptonite（SUVH 4/KYP），作为TrAP的真正细胞靶点。TrAP与KYP的催化结构域相互作用并抑制其体外活性。TrAP诱发发育异常，表型复制几个TGS突变体，减少抑制性H3 K9 me 2标记和CHH DNA甲基化，并在体内重新激活许多内源性KYP抑制基因座。此外，KYP与病毒染色质结合并控制其甲基化以对抗病毒感染。值得注意的是，kyp突变体支持TrAP缺陷型双生病毒的全身感染。我们得出结论，TrAP通过抑制KYP活性来减弱病毒染色质的TGS，以逃避宿主的监视。这些发现为宿主抗病毒防御和病毒反防御之间的分子军备竞赛提供了新的见解。DOI：http://dx.doi.org/10.7554/eLife.06671.001许多病毒可以感染植物并引起疾病，从而降低作物产量。双生病毒属是植物病毒的一个家族，由昆虫传播，感染番茄、卷心菜和许多其他作物。这些病毒劫持它们感染的植物细胞，并迫使植物细胞利用病毒自身DNA中的基因提供的指令制造病毒蛋白质。为了制造蛋白质，DNA首先被复制成信使核糖核酸（或mRNA）的分子，这一过程称为转录。然而，植物可以通过“转录基因沉默”阻断病毒DNA的转录来保护自己。在植物细胞中，DNA被包装在一种叫做组蛋白的蛋白质周围，形成一种叫做染色质的结构。附着在组蛋白上的小的化学标签可以改变染色质的结构，从而调节其中编码的基因的活性。例如，添加到某些组蛋白上的“甲基”标签可以阻止转录并降低基因的活性。来自病毒的DNA也可以与植物细胞内的组蛋白结合，这意味着转录基因沉默可以通过添加这些甲基标签而发生。许多双生病毒产生一种名为TrAP的蛋白质，它可以激活转录，但尚不清楚这是如何工作的。Castillo-González等人研究了来自两种不同双生病毒的TrAP蛋白，它们可以感染作物植物。通常使用的模式植物，拟南芥，基因工程产生高水平的这些TrAP蛋白。这些“转基因”植物没有正常发育：它们生长得更慢，叶子不正常，开花更早。此外，在转基因植株中，数百个植物基因比平常更活跃，这表明TrAP抑制转录基因沉默。进一步的实验表明，TrAP直接与一种叫做KYP的植物酶结合，这种酶通常会在染色质上沉积甲基，并阻止它发挥作用。这减少了与病毒和植物染色质相关的组蛋白连接的甲基基团的数量，这导致了通常被关闭的基因的激活。卡斯蒂略-冈萨雷斯等人的发现显示了双生病毒如何阻止含有病毒DNA的染色质的转录基因沉默，以逃避宿主植物的防御。下一个挑战是了解TrAP如何抑制KYP，这可能会为基因工程植物提供新的方法，使其对病毒感染具有抵抗力。DOI：http://dx.doi.org/10.7554/eLife.06671.002网站
Transcriptional gene silencing (TGS) can serve as an innate immunity against invading DNA viruses throughout Eukaryotes. Geminivirus code for TrAP protein to suppress the TGS pathway. Here, we identified an Arabidopsis H3K9me2 histone methyltransferase, Su(var)3-9 homolog 4/Kryptonite (SUVH4/KYP), as a bona fide cellular target of TrAP. TrAP interacts with the catalytic domain of KYP and inhibits its activity in vitro. TrAP elicits developmental anomalies phenocopying several TGS mutants, reduces the repressive H3K9me2 mark and CHH DNA methylation, and reactivates numerous endogenous KYP-repressed loci in vivo. Moreover, KYP binds to the viral chromatin and controls its methylation to combat virus infection. Notably, kyp mutants support systemic infection of TrAP-deficient Geminivirus. We conclude that TrAP attenuates the TGS of the viral chromatin by inhibiting KYP activity to evade host surveillance. These findings provide new insight on the molecular arms race between host antiviral defense and virus counter defense at an epigenetic level. DOI: http://dx.doi.org/10.7554/eLife.06671.001 Many viruses can infect plants and cause diseases that can reduce crop yields. The Geminiviruses are a family of plant viruses that are transmitted by insects and infect tomato, cabbage, and many other crop plants. These viruses hijack the plant cells that they infect and force the plant cells to make viral proteins using instructions provided by the genes in the virus' own DNA. To make proteins, DNA is first copied into molecules of messenger ribonucleic acid (or mRNA) in a process called transcription. However, plants can defend themselves by blocking the transcription of viral DNA through ‘transcriptional gene silencing’. In plant cells, DNA is packaged around proteins called histones to form a structure called chromatin. Small chemical tags attached to the histones can alter the structure of chromatin to regulate the activity of the genes encoded within it. For example, ‘methyl’ tags added to certain histones can block transcription and lower the activity of a gene. DNA from viruses can also associate with histones inside plant cells meaning that transcriptional gene silencing can take place by the addition of these methyl tags. Many Geminiviruses produce a protein called TrAP, which can activate transcription, but it is not clear how this works. Castillo-González et al. studied the TrAP proteins from two different Geminiviruses that can infect crop plants. The commonly used model plant, Arabidopsis thaliana, was genetically engineered to produce high levels of these TrAP proteins. These ‘transgenic’ plants did not develop properly: they grew more slowly, had abnormal leaves, and flowered earlier. Furthermore, hundreds of plant genes were more active than usual in the transgenic plants, which suggests that TrAP inhibits transcriptional gene silencing. Further experiments showed that TrAP directly binds to a plant enzyme called KYP—which normally deposits methyl groups on chromatin and prevents it from working. This reduces the number of methyl groups that are attached to histones associated with both viral and plant chromatin, which results in the activation of genes that would normally be switched off. Castillo-González et al.'s findings show how Geminiviruses can stop transcriptional gene silencing of chromatin that contains virus DNA to evade the host plant's defenses. The next challenge is to understand how TrAP inhibits KYP, which may present new ways to genetically engineer plants to become resistant to infection by viruses. DOI: http://dx.doi.org/10.7554/eLife.06671.002