title: Epigenetic transcriptional repression of cellular genes by a viral SET protein.
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.
authors.affiliation: Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York University, 1425 Madison Avenue, Box 1677, New York, NY 10029, USA.
authors.forename: Shiraz
authors.initials: S
authors.lastname: Mujtaba
authors.forename: Karishma L
authors.initials: KL
authors.lastname: Manzur
authors.forename: James R
authors.initials: JR
authors.lastname: Gurnon
authors.forename: Ming
authors.initials: M
authors.lastname: Kang
authors.forename: James L
authors.initials: JL
authors.lastname: Van Etten
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Zhou
mesh_terms: D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics; D002708:Chlorella / Q000166:cytology / Q000235:genetics* / Q000821:virology; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008745:Methylation; D008969:Molecular Sequence Data; D017862:Phycodnaviridae / Q000201:enzymology*; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*; D014771:Virion / Q000201:enzymology
chemical_list: D006657:Histones; D012097:Repressor Proteins; D014764:Viral Proteins; D011495:Histone-Lysine N-Methyltransferase