Epigenetic transcriptional repression of cellular genes by a viral SET protein

Shiraz Mujtaba, Karishma L. Manzur, James R. Gurnon, Ming Kang, James L. Van Etten, Ming Ming Zhou

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Viruses recruit host proteins to secure viral genome maintenance and replication. However, whether they modify host histones directly to interfere with chromatin-based transcription is unknown. Here we report that Paramecium bursaria chlorella virus 1 (PBCV-1) encodes a functional SET domain histone Lys methyltransferase (HKMTase) termed vSET, which is linked to rapid inhibition of host transcription after viral infection. We show that vSET is packaged in the PBCV-1 virion, and that it contains a nuclear localization signal and probably represses host transcription by methylating histone H3 at Lys 27 (H3K27), a modification known to trigger gene silencing in eukaryotes. We also show that vSET induces cell accumulation at the G2/M phase by recruiting the Polycomb repressive complex CBX8 to the methylated H3K27 site in a heterologous system. vSET-like proteins that have H3K27 methylation activity are conserved in chlorella viruses. Our findings suggest a viral mechanism to repress gene transcription by direct modification of chromatin by PBCV-1 vSET.

Original languageEnglish (US)
Pages (from-to)1114-1122
Number of pages9
JournalNature Cell Biology
Volume10
Issue number9
DOIs
StatePublished - Aug 20 2008

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Epigenetic Repression
Viral Proteins
Chlorella
Paramecium
Viruses
Genes
Histones
Chromatin
Nuclear Localization Signals
G2 Phase
Viral Genome
Gene Silencing
Virus Diseases
Eukaryota
Virion
Cell Division
Methylation
Proteins
Maintenance

ASJC Scopus subject areas

  • Cell Biology

Cite this

Epigenetic transcriptional repression of cellular genes by a viral SET protein. / Mujtaba, Shiraz; Manzur, Karishma L.; Gurnon, James R.; Kang, Ming; Van Etten, James L.; Zhou, Ming Ming.

In: Nature Cell Biology, Vol. 10, No. 9, 20.08.2008, p. 1114-1122.

Research output: Contribution to journalArticle

Mujtaba, S, Manzur, KL, Gurnon, JR, Kang, M, Van Etten, JL & Zhou, MM 2008, 'Epigenetic transcriptional repression of cellular genes by a viral SET protein', Nature Cell Biology, vol. 10, no. 9, pp. 1114-1122. https://doi.org/10.1038/ncb1772
Mujtaba, Shiraz ; Manzur, Karishma L. ; Gurnon, James R. ; Kang, Ming ; Van Etten, James L. ; Zhou, Ming Ming. / Epigenetic transcriptional repression of cellular genes by a viral SET protein. In: Nature Cell Biology. 2008 ; Vol. 10, No. 9. pp. 1114-1122.
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