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Trimethylation of histone H3 lysine 4 by Set1 in the lytic infection of human herpes simplex virus 1
被引:89
作者:
Huang, Jing
Kent, Jennifer R.
Placek, Brandon
Whelan, Kelly A.
Hollow, Charles A.
Zeng, Ping-Yao
Fraser, Nigel W.
Berger, Shelley L.
机构:
[1] Wistar Inst Anat & Biol, Gene Express & Regulat Program, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
关键词:
D O I:
10.1128/JVI.00169-06
中图分类号:
Q93 [微生物学];
学科分类号:
071005 ;
100705 ;
摘要:
Human herpes simplex virus 1 (HSV-1) is a double-stranded DNA virus that causes facial, ocular, and encephalitic disease in humans. Previous work showed that the genome of HSV-1 is associated with acetylated and methyllated histones during lytic infection. However, the physiological role of histone modifications in lytic infection of HSV-1 is unclear. We examined the role of protein methylation in lytic infection of HSV-1 using a protein methylation inhibitor, 5'-deoxy-5'-methylthioadenosine (MTA). We found that MTA strongly reduces the transcription and replication of HSV-1. Moreover, MTA treatment decreases the level of trimethylation of lysine 4 in histone H3 (H3K4me3) on the HSV-1 genome. These results suggest that protein methylation, and in particular, histone methylation, is involved in the lytic infection of HSV-1. To delineate the underlying mechanism, we investigated the role of two H3K4 methyltransferases, Sell and Set7/9, in the lytic infection of HSV-1. Using small interference RNA, we found that the reduction of Sell, but not Set7/9, reduces the transcription and replication of HSV-1 and specifically decreases H3K4me3 on the virus genome. These results indicate that H3K4me3 mediated by Sett is required for optimal gene expression and replication of HSV-1 during lytic infection and suggest that this pathway could be a potential point of pharmacological intervention during HSV-1 infection.
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页码:5740 / 5746
页数:7
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