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Blood, 15 January 2005, Vol. 105, No. 2, pp. 711-720. Prepublished online as a Blood First Edition Paper on September 2, 2004; DOI 10.1182/blood-2004-03-0842. This Article Full Text (PDF) All Versions of this Article: 2004-03-0842v1 105/2/711    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Musikacharoen, T. Articles by Matsuguchi, T. Search for Related Content PubMed PubMed Citation Articles by Musikacharoen, T. Articles by Matsuguchi, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 5, 2004 Accepted August 26, 2004 Interleukin-15 induces IL-12 receptor 1 gene expression through PU.1 and IRF 3 by targeting chromatin remodeling Tipayaratn Musikacharoen, Asako Oguma, Yasunobu Yoshikai, Norika Chiba, Akio Masuda, and Tetsuya Matsuguchi* Department of Developmental Medicine, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan Division of Host Defense, Center for Neural Disease and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan Division of Host Defense, Research Center of Prevention of Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan * Corresponding author; email: tmatsugu{at}denta.hal.kagoshima-u.ac.jp. Interleukin-12 receptor 1 (IL-12R1) is expressed on a variety of immune cells including T/NK cells and macrophages, and involved in both innate and adaptive immune responses. Levels of IL-12R1 mRNA are dynamically regulated by various cytokines including interferon-(IFN-) and IL-15. To reveal the regulatory mechanisms governing IL-12R1 gene expression, we analyzed the transcriptional regulatory region of the mouse IL-12R1 gene. Promoter analyses in a mouse macrophage cell line, RAW264.7, revealed that the 2508bp region upstream of the transcriptional start site is sufficient for the full transcriptional activation of the IL-12R1 gene by either IFN- or IL-15. Analyses of the deletion mutants revealed critical roles of IRE/ISRE and ETS/PU.1 elements, to which IRF3 and PU.1 respectively bound. Notably, chromatin immunoprecipitation (ChIP) assays revealed IL-15 rapidly induced histone H3 acetylation at the IL-12R1 promoter. Consistently, IL-15, like a histone deacetylase inhibitor, synergistically enhanced IL-12R1 gene expression and promoter activation by IFN- through increased protein binding to both ETS/PU.1 and IRE/ISRE sites. Additionally, IL-12R1 promoter activation by IFN- was enhanced by the co-expression of a co-activator protein, CBP. Thus IL-15 induces chromatin remodeling of the IL-12R1 gene promoter increasing IL-12R1 mRNA expression in synergy with IFN- through recruitment of PU.1 and IRF3. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Mizubuchi, T. Yajima, N. Aoi, T. Tomita, and Y. Yoshikai Isomalto-Oligosaccharides Polarize Th1-Like Responses in Intestinal and Systemic Immunity in Mice J. Nutr., December 1, 2005; 135(12): 2857 - 2861. [Abstract] [Full Text] [PDF]

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