title: p300, but not PCAF, collaborates with IRF-1 in stimulating TRIM22 expression independently of its histone acetyltransferase activity.
abstract: Tripartite motif (TRIM) 22 plays an important role in IFN-mediated antiviral activity. We previously demonstrated that IFN regulatory factor-1 (IRF-1) was crucial for constitutive and IFN-induced TRIM22 expression via binding to a special cis-element named 5' extended IFN-stimulating response element. Here, we further investigate the molecular mechanisms of TRIM22 with a focus on the co-activators of IRF-1. Using an in vitro DNA affinity binding assay and an in vivo chromatin immunoprecipitation assay, we found that IFN-γ stimulation significantly enhanced the binding of p300 and p300/CBP-associated factor, but not other co-activators such as general control nondepressible 5, steroid receptor co-activator-1, and activator of thyroid and retinoic, to the 5' extended IFN-stimulating response element containing TRIM22 promoter region together with IRF-1. Overexpression and knockdown analysis demonstrated that it was p300, but not p300/CBP-associated factor, that functioned as a transcriptional co-activator of IRF-1 in IFN-γ induction of TRIM22. We further show that p300 contributed to both IFN-γ- and IRF-1-mediated TRIM22 transcription independent of its histone acetyltransferase activity, however, it was required for the recruitment of RNA polymerase II to TRIM22 promoter region. These data indicate that p300 plays a critical role in IFN-γ-induced TRIM22 expression via recruiting RNA polymerase II to the TRIM22 promoter, and might serve as a bridge between IRF-1 and the basal transcriptional apparatus in TRIM22 induction.
authors.affiliation: Department of Immunology, Institute for Immunobiology, Shanghai Medical College of Fudan University, Shanghai, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Linmao
authors.initials: L
authors.lastname: Zhong
authors.forename: Qilin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ya
authors.initials: Y
authors.lastname: Su
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
mesh_terms: D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D056945:Hep G2 Cells; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D056920:Nuclear Receptor Coactivator 1 / Q000378:metabolism; D056921:Nuclear Receptor Coactivator 3 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000096:biosynthesis*; D000070584:Tripartite Motif Proteins; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D051548:Histone Acetyltransferases; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma; D015778:Minor Histocompatibility Antigens; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D012319:RNA Polymerase II; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000070584:Tripartite Motif Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C094314:TRIM22 protein, human; C538859:NCOA1 protein, human; C538866:NCOA3 protein, human
keywords: Co-activator; Histone acetyltransferase activity; IFN; TRIM22; p300