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Gene Review

Irf2  -  interferon regulatory factor 2

Mus musculus

Synonyms: 9830146E22Rik, AI646973, IRF-2, Interferon regulatory factor 2, Irf-2
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Disease relevance of Irf2


High impact information on Irf2

  • The transcriptional activator interferon regulatory factor 1 (IRF-1) and its antagonistic repressor IRF-2 are regulators of the interferon (IFN) system and of cell growth [6].
  • In contrast, IRF-2-deficient fibroblasts showed up-regulated type I IFN induction by NDV infection [2].
  • CD8(+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-alpha/beta signaling [7].
  • IRF-2 may represent a unique negative regulator, attenuating IFN-alpha/beta-induced gene transcription, which is necessary for balancing the beneficial and harmful effects of IFN-alpha/beta signaling in the immune system [7].
  • We show that the IRF-2 oncoprotein represses virus-induced IFN-beta gene transcription via a novel mechanism [8].

Biological context of Irf2

  • Furthermore, we observed using reverse transcription-polymerase chain reaction that the IRF-1 mRNA expression was more abundant in confluent cells than growing cells, whereas IRF-2 expression did not change with R3T3 cell growth [9].
  • TPA treatment leads to recruitment of IRF-2 to 32kb-150 of the endogenous NMHC-A gene and acetylation of the core histones surrounding this region [10].
  • IRF-2 is involved in up-regulation of nonmuscle myosin heavy chain II-A gene expression during phorbol ester-induced promyelocytic HL-60 differentiation [10].
  • IRF-2, which is known to either repress or activate target gene expression, acts as a transcriptional activator in the context of the 32kb-150 reporter gene [10].
  • Together, these results indicate that IRF-2 contributes to transcriptional activation of the NMHC-A gene via 32kb-150 during TPA-induced differentiation of HL-60 cells [10].

Anatomical context of Irf2

  • Furthermore, after treatment of promyelocytic HL-60 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), which triggers differentiation into macrophages, both NMHC-A expression and IRF-2 expression were found to be up-regulated with a similar time course [10].
  • We further show that in the developing mouse lens, IRF-1 and IRF-2 are expressed at high levels in differentiated lens fiber cells with very low and barely detectable levels in undifferentiated lens epithelial cells [11].
  • Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development [2].
  • We have generated mice deficient in either IRF-1 or IRF-2 by gene targeting in embryonic stem cells [2].
  • NK (but not NK(+) T) cell numbers are decreased in IRF-2(-/)- mice, and the NK cells that are present are immature in phenotype [3].

Associations of Irf2 with chemical compounds


Physical interactions of Irf2

  • Chromatin immunoprecipitation assays showed that IRF-2 interacted with p300 and bound to the endogenous H4 promoter only in growing cells, although the levels of total IRF-2 were comparable in both growing and growth-arrested cells [16].
  • IRF-1 functions as an activator whereas IRF-2 binds to the same cis-elements and can repress IRF-1 action [17].

Regulatory relationships of Irf2


Other interactions of Irf2


Analytical, diagnostic and therapeutic context of Irf2


  1. Crucial role of interferon consensus sequence binding protein, but neither of interferon regulatory factor 1 nor of nitric oxide synthesis for protection against murine listeriosis. Fehr, T., Schoedon, G., Odermatt, B., Holtschke, T., Schneemann, M., Bachmann, M.F., Mak, T.W., Horak, I., Zinkernagel, R.M. J. Exp. Med. (1997) [Pubmed]
  2. Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development. Matsuyama, T., Kimura, T., Kitagawa, M., Pfeffer, K., Kawakami, T., Watanabe, N., Kündig, T.M., Amakawa, R., Kishihara, K., Wakeham, A. Cell (1993) [Pubmed]
  3. Deficiency in the transcription factor interferon regulatory factor (IRF)-2 leads to severely compromised development of natural killer and T helper type 1 cells. Lohoff, M., Duncan, G.S., Ferrick, D., Mittrücker, H.W., Bischof, S., Prechtl, S., Röllinghoff, M., Schmitt, E., Pahl, A., Mak, T.W. J. Exp. Med. (2000) [Pubmed]
  4. Susceptibility of IFN regulatory factor-1 and IFN consensus sequence binding protein-deficient mice to brucellosis. Ko, J., Gendron-Fitzpatrick, A., Splitter, G.A. J. Immunol. (2002) [Pubmed]
  5. Characterization of the DNA binding domain of the mouse IRF-2 protein. Uegaki, K., Shirakawa, M., Fujita, T., Taniguchi, T., Kyogoku, Y. Protein Eng. (1993) [Pubmed]
  6. Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1. Tanaka, N., Ishihara, M., Kitagawa, M., Harada, H., Kimura, T., Matsuyama, T., Lamphier, M.S., Aizawa, S., Mak, T.W., Taniguchi, T. Cell (1994) [Pubmed]
  7. CD8(+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-alpha/beta signaling. Hida, S., Ogasawara, K., Sato, K., Abe, M., Takayanagi, H., Yokochi, T., Sato, T., Hirose, S., Shirai, T., Taki, S., Taniguchi, T. Immunity (2000) [Pubmed]
  8. Gene repression by coactivator repulsion. Senger, K., Merika, M., Agalioti, T., Yie, J., Escalante, C.R., Chen, G., Aggarwal, A.K., Thanos, D. Mol. Cell (2000) [Pubmed]
  9. The growth-dependent expression of angiotensin II type 2 receptor is regulated by transcription factors interferon regulatory factor-1 and -2. Horiuchi, M., Koike, G., Yamada, T., Mukoyama, M., Nakajima, M., Dzau, V.J. J. Biol. Chem. (1995) [Pubmed]
  10. IRF-2 is involved in up-regulation of nonmuscle myosin heavy chain II-A gene expression during phorbol ester-induced promyelocytic HL-60 differentiation. Chung, M.C., Kawamoto, S. J. Biol. Chem. (2004) [Pubmed]
  11. Interferon regulatory transcription factors are constitutively expressed and spatially regulated in the mouse lens. Li, W., Nagineni, C.N., Efiok, B., Chepelinsky, A.B., Egwuagu, C.E. Dev. Biol. (1999) [Pubmed]
  12. The role of the interferon regulatory factors, IRF-1 and IRF-2, in LPS-induced cyclooxygenase-2 (COX-2) expression in vivo and in vitro. Zhang, S., Thomas, K., Blanco, J.C., Salkowski, C.A., Vogel, S.N. J. Endotoxin Res. (2002) [Pubmed]
  13. Interferon regulatory factor-1 up-regulates angiotensin II type 2 receptor and induces apoptosis. Horiuchi, M., Yamada, T., Hayashida, W., Dzau, V.J. J. Biol. Chem. (1997) [Pubmed]
  14. Forced expression of the interferon regulatory factor 2 oncoprotein causes polyploidy and cell death in FDC-P1 myeloid hematopoietic progenitor cells. Xie, R.L., van Wijnen, A.J., van der Meijden, C.M., Stein, J.L., Stein, G.S. Cancer Res. (2002) [Pubmed]
  15. Differential dysregulation of nitric oxide production in macrophages with targeted disruptions in IFN regulatory factor-1 and -2 genes. Salkowski, C.A., Barber, S.A., Detore, G.R., Vogel, S.N. J. Immunol. (1996) [Pubmed]
  16. Interferon regulatory factor-2 regulates cell growth through its acetylation. Masumi, A., Yamakawa, Y., Fukazawa, H., Ozato, K., Komuro, K. J. Biol. Chem. (2003) [Pubmed]
  17. The oncogenic transcription factor IRF-2 possesses a transcriptional repression and a latent activation domain. Yamamoto, H., Lamphier, M.S., Fujita, T., Taniguchi, T., Harada, H. Oncogene (1994) [Pubmed]
  18. IFN-gamma induces the kappa intron enhancer via an IFN-stimulated response element. Damore, M.A., Omori, S.A., Wall, R. J. Immunol. (1996) [Pubmed]
  19. Interferon regulatory factor-2 is a transcriptional activator in muscle where It regulates expression of vascular cell adhesion molecule-1. Jesse, T.L., LaChance, R., Iademarco, M.F., Dean, D.C. J. Cell Biol. (1998) [Pubmed]
  20. IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice. Salkowski, C.A., Kopydlowski, K., Blanco, J., Cody, M.J., McNally, R., Vogel, S.N. J. Immunol. (1999) [Pubmed]
  21. Impaired class II transactivator expression in mice lacking interferon regulatory factor-2. Xi, H., Goodwin, B., Shepherd, A.T., Blanck, G. Oncogene (2001) [Pubmed]
  22. Regulation of lipopolysaccharide sensitivity by IFN regulatory factor-2. Cuesta, N., Salkowski, C.A., Thomas, K.E., Vogel, S.N. J. Immunol. (2003) [Pubmed]
  23. Negative control of basophil expansion by IRF-2 critical for the regulation of Th1/Th2 balance. Hida, S., Tadachi, M., Saito, T., Taki, S. Blood (2005) [Pubmed]
  24. Characterization of a novel IRF-1-deficient mutant cell line. Lim, S.P., Hui, K.M. Immunogenetics (1994) [Pubmed]
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