CpG methylation directly regulates transcriptional activity of the human endogenous retrovirus family HERV-K(HML-2)

被引：168

作者：

Lavie, L ^{[1
]}

Kitova, M ^{[1
]}

Maldener, E ^{[1
]}

Meese, E ^{[1
]}

Mayer, J ^{[1
]}

机构：

[1] Univ Saarland, Dept Human Genet, Fac Med, D-66421 Homburg, Germany

来源：

JOURNAL OF VIROLOGY | 2005年 / 79卷 / 02期

关键词：

D O I：

10.1128/JVI.79.2.876-883.2005

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

A significant proportion of the human genome consists of stably inherited retroviral sequences. Most human endogenous retroviruses (HERVs) became defective over time. The HERV-K(HML-2) family is exceptional because of its coding capacity and the possible involvement in germ cell tumor (GCT) development. HERVK(HML-2) transcription is strongly upregulated in GCTs. However, regulation of HERV-K(HML-2) transcription remains poorly understood. We investigated in detail the role of CpG methylation on the transcriptional activity of HERV-K(HML-2) long terminal repeats (LTRs). We find that CpG sites in various HERVK(HML-2) proviral 5' LTRs are methylated at different levels in the cell line Tera-1. Methylation levels correlate with previously observed transcriptional activities of these proviruses. CpG-mediated silencing of HERV-K(HML-2) LTRs is further corroborated by transcriptional inactivity of in vitro-methylated 5' LTR reporter plasmids. However, CpG methylation levels do not solely regulate HERV-K(HML-2) 5' LTR activity, as evidenced by different LTR activities in the cell line T47D. A significant number of mutated CpG sites in evolutionary old HERV-K(HML-2) 5' LTRs suggests that CpG methylation had already silenced HERVK(HML-2) proviruses millions of years ago. Direct silencing of HERV-K(HML-2) expression by CpG methylation enlightens upregulated HERV-K(HML-2) expression in usually hypomethylated GCT tissue.

引用

页码：876 / 883

页数：8

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