Epigenetic transcriptional repression of cellular genes by a viral SET protein

Authors

Shiraz Mujtaba, Mount Sinai School of Medicine, New York University
Karishma L. Manzur, Mount Sinai School of Medicine, New York University
James Gurnon, University of Nebraska-LincolnFollow
Ming Kang, University of Nebraska-LincolnFollow
James L. Van Etten, University of Nebraska-LincolnFollow
Ming-Ming Zhou, Mount Sinai School of Medicine, New York UniversityFollow

Document Type

Article

Date of this Version

9-2008

Comments

Published in Nature Cell Biology 10:9 (September 2008), pp. 1114 - 1122; doi:10.1038/ncb1772 Copyright © 2008 Macmillan Publishers Ltd. Used by permission.

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.