Interferon-stimulated transcription and innate antiviral immunity require deacetylase activity and histone deacetylase 1

Inna Nusinzon, Curt M. Horvath*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

210 Scopus citations

Abstract

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-α stimulation induces deacetylation of histone H4. Inhibition of HDAC1 by small interfering RNA (siRNA) decreases IFN-α responsiveness whereas expression of HDAC1 augments the IFN-α response, demonstrating that HDAC1 modulates IFN-α-induced transcription. Importantly, the innate antiviral response is inhibited in the absence of deacetylase activity. The requirement for deacetylase is shared by IFN-γ transcription response and may represent a general requirement for STAT-dependent gene expression.

Original languageEnglish (US)
Pages (from-to)14742-14747
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number25
DOIs
StatePublished - Dec 9 2003

ASJC Scopus subject areas

  • General

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