Letter abstract
Nature Cell Biology 10, 1114 - 1122 (2008)
Published online: 17 August 2008 | doi:10.1038/ncb1772
Epigenetic transcriptional repression of cellular genes by a viral SET protein
Shiraz Mujtaba1, Karishma L. Manzur1, James R. Gurnon2, Ming Kang2, James L. Van Etten2 & Ming-Ming Zhou1
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.
- Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York University, 1425 Madison Avenue, Box 1677, New York, NY 10029, USA.
- Department of Plant Pathology and Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska 68583, USA.
Correspondence to: Ming-Ming Zhou1 e-mail: ming-ming.zhou@mssm.edu
Correspondence to: James L. Van Etten2 e-mail: jvanetten@unlnotes.unl.edu
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