Interferon-stimulated transcription and innate antiviral immunity require deacetylase activity and histone deacetylase 1.
The use of histone deacetylase (HDAC) inhibitors has revealed an essential role for deacetylation in transcription of IFN-responsive genes. The HDAC1 protein associates with both signal transducer and activator of transcription (STAT) 1 and STAT2, and IFN-alpha stimulation induces deacetylation of histone H4. Inhibition of HDAC1 by small interfering RNA (siRNA) decreases IFN-alpha responsiveness whereas expression of HDAC1 augments the IFN-alpha response, demonstrating that HDAC1 modulates IFN-alpha-induced transcription. Importantly, the innate antiviral response is inhibited in the absence of deacetylase activity. The requirement for deacetylase is shared by IFN-gamma transcription response and may represent a general requirement for STAT-dependent gene expression.
Nusinzon
Inna
I
Immunobiology Center, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1630, New York, NY 10029, USA.
Horvath
Curt M
CM
D000107:Acetylation; D021581:Active Transport, Cell Nucleus; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D017930:Genes, Reporter; D006367:HeLa Cells; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014777:Virus Diseases / Q000276:immunology*
D002843:Chromatin; D016207:Cytokines; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006657:Histones; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D012313:RNA; D007371:Interferon-gamma; D004247:DNA; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases