Castillo-González Claudia, Liu Xiuying, Huang Changjun, Zhao Changjiang, Ma Zeyang, Hu Tao, Sun Feng, Zhou Yijun, Zhou Xueping, Wang Xiu-Jie, Zhang Xiuren
Department of Biochemistry and Biophysics, Texas A&M University, College Station, United States.
Institute for Plant Genomics and Biotechnology, Texas A&M University, College Station, United States.
Elife. 2015 Sep 7;4:e06671. doi: 10.7554/eLife.06671.
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.
转录基因沉默（TGS）可作为真核生物对入侵DNA病毒的一种固有免疫。双生病毒编码TrAP蛋白以抑制TGS途径。在此，我们鉴定出拟南芥H3K9me2组蛋白甲基转移酶，Su(var)3-9同源物4/氪石（SUVH4/KYP），作为TrAP真正的细胞靶点。TrAP与KYP的催化结构域相互作用并在体外抑制其活性。TrAP引发的发育异常模拟了几个TGS突变体，减少了抑制性的H3K9me2标记和CHH DNA甲基化，并在体内重新激活了许多内源性KYP抑制的基因座。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突变体支持缺乏TrAP的双生病毒的系统感染。我们得出结论，TrAP通过抑制KYP活性来减弱病毒染色质的TGS，从而逃避宿主监测。这些发现为宿主抗病毒防御与病毒在表观遗传水平上的反防御之间的分子军备竞赛提供了新的见解。
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