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 journalArticlepeer-review

48 Scopus citations

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 - 2008

ASJC Scopus subject areas

  • Cell Biology

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