title: Histone deacetylase activity is required to recruit RNA polymerase II to the promoters of selected interferon-stimulated early response genes.
abstract: Posttranslational modification of histones by acetylation, methylation or phosphorylation has emerged as a major mechanism to modify chromatin structure and gene expression. In most cases, transcriptionally active genes display enhanced binding of acetylated histones in their promoters. Activation of histone acetyltransferases or inhibition of histone deacetylases (HDACs) allows chromatin to assume a more open state permitting transcriptional activators to form a preinitiation complex. To our surprise, treatment of cells with the HDAC inhibitor, trichostatin A (TSA), inhibits selected interferon beta (IFNbeta)-stimulated immediate early genes that are activated by the transcription factors Stat1 and Stat2. However, IFNbeta activation of IRF-1, which requires tyrosine-phosphorylated Stat1 homodimers binding to a gamma interferon activation sequence in its promoter is not affected by TSA. Exposure of cells to TSA does not alter tyrosine phosphorylation of Stat1 or Stat2. TSA treatment of cells also does not alter the binding of Stat 1 or Stat2 to the endogenous ISG54 promoter. However, IFNbeta-stimulated binding of RNA polymerase II to the ISG54 promoter is prevented by TSA. Interestingly, ectopic expression of IRF9 reverses the inhibitory actions of TSA, suggesting that IRF9 functions to recruit RNA polymerase II to the promoter of interferon-stimulated genes. This particular function of IRF9 requires the activity of histone deacetylases.
authors.affiliation: Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: Shuji
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Ramesh
authors.initials: R
authors.lastname: Potla
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Larner
mesh_terms: D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D019281:Dimerization; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D050856:Interferon Regulatory Factor-1; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016899:Interferon-beta / Q000378:metabolism; D007372:Interferons / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism / Q000502:physiology*; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006877:Hydroxamic Acids; C494257:IRF1 protein, human; C494227:IRF9 protein, human; D050856:Interferon Regulatory Factor-1; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D010750:Phosphoproteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C012589:trichostatin A; D014443:Tyrosine; D016899:Interferon-beta; D007372:Interferons; D008156:Luciferases; D012319:RNA Polymerase II; D006655:Histone Deacetylases