The EBV lytic switch protein, Z, preferentially binds to and activates the methylated viral genome

被引：150

作者：

Bhende, PM

Seaman, WT

Delecluse, HJ

Kenney, SC ^{[1
]}

机构：

[1] Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA

[2] Univ N Carolina, Dept Microbiol, Chapel Hill, NC USA

[3] Univ N Carolina, Dept Immunol, Chapel Hill, NC USA

[4] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[5] German Canc Res Ctr, Dept Virus Associated Tumours, D-6900 Heidelberg, Germany

来源：

NATURE GENETICS | 2004年 / 36卷 / 10期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/ng1424

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

DNA methylation promotes gene silencing, yet the Epstein-Barr virus immediate-early protein, BZLF1 (Z), converts the virus from the latent to the lytic form of infection even when the viral genome is highly methylated. Here we show that methylation of CpG motifs in Z-responsive elements of the viral BRLF1 immediate-early promoter enhances Z binding to, and activation of, this promoter. Demethylation of the viral genome impairs Z activation of lytic viral genes. Z is the first transcription factor that preferentially binds to, and activates, a methylated promoter. These results identify an unexpected mechanism by which Epstein-Barr virus circumvents the inhibitory effects of viral genome methylation.

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页码：1099 / 1104

页数：6

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