Induction of interferon-stimulated gene expression and antiviral responses require protein deacetylase activity.
Histone deacetylase (HDAC) activity, commonly correlated with transcriptional repression, was essential for transcriptional induction of IFN-stimulated genes (ISG). Inhibition of HDAC function led to global impairment of ISG expression, with little effect on basal expression. HDAC function was not required for signal transducer and activator of transcription tyrosine phosphorylation, nuclear translocation, or assembly on chromatin, but it was needed for full activity of the signal transducer and activator of transcription transactivation domain. HDAC function was also required for gene induction driven by the IFN regulatory factor 3 transcription factor activated by virus infection, and it was essential for establishment of an antiviral response against Flaviviridae, Rhabdoviridae, and Picornaviridae. Requirement for HDAC function in transcriptional activation may represent a general mechanism for rapid stimulation of ISG transcription.
Chang
Hao-Ming
HM
Department of Pathology and NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, NY 10016,USA.
Paulson
Matthew
M
Holko
Michelle
M
Rice
Charles M
CM
Williams
Bryan R G
BR
Marié
Isabelle
I
Levy
David E
DE
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D004686:Encephalomyocarditis virus / Q000187:drug effects / Q000472:pathogenicity; D005786:Gene Expression Regulation / Q000187:drug effects*; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D007372:Interferons / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000502:physiology
D000998:Antiviral Agents; D002843:Chromatin; D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D007372:Interferons; D006655:Histone Deacetylases