PMID:16581785

Citation	Nusinzon, I and Horvath, CM (2006) Positive and negative regulation of the innate antiviral response and beta interferon gene expression by deacetylation. Mol. Cell. Biol. 26:3106-13
Abstract	Beta interferon (IFN-beta) gene expression in response to virus infection relies on the dynamic assembly of a multiprotein enhanceosome complex that is initiated by the activation of two inducible transcription factors, interferon regulatory factor 3 (IRF3) and NF-kappaB. Virus or double-stranded RNA-induced activation of IFN-beta gene expression is prevented by the addition of protein deacetylase inhibitors. The isolated IRF-responsive positive regulatory domain was found to require deacetylation for its activity, but IRF3 protein activation leading to its nuclear translocation and DNA binding was not impaired by deacetylase inhibition. In contrast, NF-kappaB activity was not affected by deacetylase inhibitors. RNA interference indicated that several deacetylase enzymes, including histone deacetylase 1 (HDAC1), HDAC8, and HDAC6, influence IFN-beta gene expression with opposing effects. While HDAC1 and HDAC8 repress IFN-beta expression, HDAC6 acts as a coactivator essential for enhancer activity. Virus replication is enhanced in HDAC6-depleted cells, demonstrating HDAC6 is an essential component of innate antiviral immunity.
Links	PubMed PMC1446935 Online version:10.1128/MCB.26.8.3106-3113.2006
Keywords	Cell Line, Tumor; Chromatin Immunoprecipitation; Enzyme Inhibitors/pharmacology; Gene Expression Regulation; Genes, Reporter; Green Fluorescent Proteins/metabolism; HeLa Cells; Histone Deacetylase 1; Histone Deacetylase Inhibitors; Histone Deacetylases/metabolism; Histone Deacetylases/physiology; Humans; Hydroxamic Acids/pharmacology; Immunity, Innate; Interferon Regulatory Factor-3/metabolism; Interferon-beta/metabolism; NF-kappa B/metabolism; Plasmids/metabolism; RNA Interference; Repressor Proteins/metabolism; Sendai virus/metabolism; Vesicular stomatitis Indiana virus/metabolism; Virus Diseases/genetics; Virus Diseases/immunology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:HDAC1		GO:0010629: negative regulation of gene expression	ECO:0000315:		P		Figure 3: Acts as a repressor of INF-beta gene expression	complete CACAO 8834
HUMAN:HDAC1	involved_in	GO:0010629: negative regulation of gene expression	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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