Transcriptional and chromatin regulation in interferon and innate antiviral gene expression

Nancy Au-Yeung, Curt M. Horvath*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations

Abstract

In response to virus infections, a cell-autonomous, transcription-based antiviral program is engaged to create resistance, impair pathogen replication, and alert professional cells in innate and adaptive immunity. This dual phase antiviral program consists of type I interferon (IFN) production followed by the response to IFN signaling. Pathogen recognition leads to activation of IRF and NFκB factors that function independently and together to recruit cellular coactivators that remodel chromatin, modify histones and activate RNA polymerase II (Pol II) at target gene loci, including the well-characterized IFNβ enhanceosome. In the subsequent response to IFN, a receptor-mediated JAK-STAT signaling cascade directs the assembly of the IRF9-STAT1-STAT2 transcription factor complex called ISGF3, which recruits its own cohort of remodelers, coactivators, and Pol II machinery to activate transcription of a wide range of IFN-stimulated genes. Regulation of the IFN and antiviral gene regulatory networks is not only important for driving innate immune responses to infections, but also may inform treatment of a growing list of chronic diseases that are characterized by hyperactive and constitutive IFN and IFN-stimulated gene (ISG) expression. Here, gene-specific and genome-wide investigations of the chromatin landscape at IFN and ISGs is discussed in parallel with IRF- and STAT- dependent regulation of Pol II transcription.

Original languageEnglish (US)
Pages (from-to)11-17
Number of pages7
JournalCytokine and Growth Factor Reviews
Volume44
DOIs
StatePublished - Dec 2018

Keywords

  • Antiviral
  • Chromatin
  • IRF
  • Interferon
  • NFκB
  • STAT
  • Transcription

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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