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Co-occupancy of the interferon regulatory element of the class II transactivator (CIITA) Type IV promoter by interferon regulatory factors 1 and 2

Oncogene volume 18, pages 5889–5903 (1999)Cite this article

Abstract

Class II transactivator (CIITA) activates the expression of major histocompatibility class II genes, which encode antigen-presenting molecules recognized by the T-cell receptor of CD4+ T cells. IFN-γ induced CIITA transcription in many cell types is directed by the CIITA Type IV promoter. Here we report that the human CIITA Type IV promoter IRF-E binds IRF-1 and can be activated by exogenous expression of IRF-1. Surprisingly, the CIITA Type IV promoter IRF-E is also activated by IRF-2, another member of the IRF family that generally acts as a transcriptional repressor. In addition, we found that IRF-1 and IRF-2 synergistically activate the CIITA Type IV promoter. Electrophoretic mobility shift assays revealed that IRF-1 and IRF-2 can simultaneously occupy the IRF-E of the CIITA Type IV promoter, suggesting a novel mechanism for the role of these two proteins in promoter activation. Our results also indicate that IRF-1 and IRF-2 can cooperatively activate and co-occupy the IRF-E of the guanylate binding protein (GBP) promoter. Finally, CIITA induction by IFN-γ does not occur in a pancreatic tumor cell line that expresses a mutated IRF-2, representing the first IRF-2 mutation identified in a human tumor cell line.

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Acknowledgements

We thank R Jove (University of South Florida) for advice on EMSA experiments. We thank M-B Colter of H Lee Moffitt Cancer Center Molecular Biology Core Facility for assistance with DNA sequencing. This work was supported by an American Heart Association of Florida grant (9601461), an American Cancer Society grant (RPG-98-184-01-CIM), and an American Lung Association of Florida grant to G Blanck.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa, 33612, Florida, FL, USA

    Hongkang Xi, Donna D Eason, Debarati Ghosh, Kenneth L Wright & George Blanck

  2. Department of Medical Microbiology and Immunology, College of Medicine, University of South Florida, Tampa, 33612, Florida, FL, USA

    Susan Dovhey

  3. Immunology Program, H Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, 33612, Florida, FL, USA

    Kenneth L Wright & George Blanck

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  1. Hongkang Xi
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Xi, H., Eason, D., Ghosh, D. et al. Co-occupancy of the interferon regulatory element of the class II transactivator (CIITA) Type IV promoter by interferon regulatory factors 1 and 2. Oncogene 18, 5889–5903 (1999). https://doi.org/10.1038/sj.onc.1202969

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