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Gene Review

Runx1  -  runt related transcription factor 1

Mus musculus

Synonyms: AI462102, AML1, Acute myeloid leukemia 1 protein, Aml1, CBF-alpha-2, ...
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Disease relevance of Runx1


Psychiatry related information on Runx1

  • Heterozygous disruption of Runx1 in BXH2 mice resulted in a shortening of the latency period of leukaemia [5].

High impact information on Runx1

  • We previously reported that mice with a deletion of an upstream regulatory element (URE) of the gene encoding PU.1 (Sfpi1) developed acute myeloid leukemia [6].
  • Examination of human individuals with AML confirmed the correlation between PU.1 and JunB downregulation [7].
  • Runx3-deficient cytotoxic T cells, but not helper cells, have defective responses to antigen, suggesting that Runx proteins have critical functions in lineage specification and homeostasis of CD8-lineage T lymphocytes [8].
  • We show here that binding sites for Runt domain transcription factors are essential for CD4 silencer function at both stages, and that different Runx family members are required to fulfill unique functions at each stage [8].
  • Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBFbeta [9].

Chemical compound and disease context of Runx1


Biological context of Runx1


Anatomical context of Runx1

  • We established embryonic stem cell clones carrying the Venus gene, a modified version of yellow fluorescence protein, in the Runx1 locus and cultured them on OP9 cells [16].
  • In peripheral T cells, Runx1 is differentially expressed, with CD4+ T cells expressing 2- to 3-fold higher levels of Runx1 than CD8+ cells [15].
  • Here we show that Runx1 represses Flk-1 during the development of hemogenic endothelial cells into hematopoietic cells [16].
  • Runx1 expression is induced during early B-cell development and is expressed at a uniform level during all subsequent stages of B-cell development [15].
  • Within the thymus, Runx1 is expressed at the highest level in CD4-CD8- double-negative thymocytes [15].

Associations of Runx1 with chemical compounds


Physical interactions of Runx1


Regulatory relationships of Runx1


Other interactions of Runx1

  • EBF function was enhanced by interaction with the transcription factor Runx1 [29].
  • Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription [29].
  • The models that have been developed should prove to be of value for defining the range of mutations that can cooperate with AML1/CBFbeta fusion proteins, and for assessing novel therapies targeted toward the pathways that are altered by the expression of these fusion proteins [30].
  • The runt family transcription factors Runx1 and Runx3 are expressed in developing murine thymocytes [31].
  • Overall, the expression of Runx1 remained significantly higher than Runx2 mRNA levels during early limb bud cell maturation [2].

Analytical, diagnostic and therapeutic context of Runx1


  1. Runx1 deficiency predisposes mice to T-lymphoblastic lymphoma. Kundu, M., Compton, S., Garrett-Beal, L., Stacy, T., Starost, M.F., Eckhaus, M., Speck, N.A., Liu, P.P. Blood (2005) [Pubmed]
  2. Runx1/AML1/Cbfa2 mediates onset of mesenchymal cell differentiation toward chondrogenesis. Wang, Y., Belflower, R.M., Dong, Y.F., Schwarz, E.M., O'Keefe, R.J., Drissi, H. J. Bone Miner. Res. (2005) [Pubmed]
  3. Core-binding factor beta interacts with Runx2 and is required for skeletal development. Yoshida, C.A., Furuichi, T., Fujita, T., Fukuyama, R., Kanatani, N., Kobayashi, S., Satake, M., Takada, K., Komori, T. Nat. Genet. (2002) [Pubmed]
  4. Cbfbeta interacts with Runx2 and has a critical role in bone development. Kundu, M., Javed, A., Jeon, J.P., Horner, A., Shum, L., Eckhaus, M., Muenke, M., Lian, J.B., Yang, Y., Nuckolls, G.H., Stein, G.S., Liu, P.P. Nat. Genet. (2002) [Pubmed]
  5. Haploinsufficiency of Runx1/AML1 promotes myeloid features and leukaemogenesis in BXH2 mice. Yamashita, N., Osato, M., Huang, L., Yanagida, M., Kogan, S.C., Iwasaki, M., Nakamura, T., Shigesada, K., Asou, N., Ito, Y. Br. J. Haematol. (2005) [Pubmed]
  6. Lymphoid cell growth and transformation are suppressed by a key regulatory element of the gene encoding PU.1. Rosenbauer, F., Owens, B.M., Yu, L., Tumang, J.R., Steidl, U., Kutok, J.L., Clayton, L.K., Wagner, K., Scheller, M., Iwasaki, H., Liu, C., Hackanson, B., Akashi, K., Leutz, A., Rothstein, T.L., Plass, C., Tenen, D.G. Nat. Genet. (2006) [Pubmed]
  7. Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells. Steidl, U., Rosenbauer, F., Verhaak, R.G., Gu, X., Ebralidze, A., Otu, H.H., Klippel, S., Steidl, C., Bruns, I., Costa, D.B., Wagner, K., Aivado, M., Kobbe, G., Valk, P.J., Passegu??, E., Libermann, T.A., Delwel, R., Tenen, D.G. Nat. Genet. (2006) [Pubmed]
  8. Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Taniuchi, I., Osato, M., Egawa, T., Sunshine, M.J., Bae, S.C., Komori, T., Ito, Y., Littman, D.R. Cell (2002) [Pubmed]
  9. Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBFbeta. Tahirov, T.H., Inoue-Bungo, T., Morii, H., Fujikawa, A., Sasaki, M., Kimura, K., Shiina, M., Sato, K., Kumasaka, T., Yamamoto, M., Ishii, S., Ogata, K. Cell (2001) [Pubmed]
  10. AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations. Yuan, Y., Zhou, L., Miyamoto, T., Iwasaki, H., Harakawa, N., Hetherington, C.J., Burel, S.A., Lagasse, E., Weissman, I.L., Akashi, K., Zhang, D.E. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  11. Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412. Growney, J.D., Clark, J.J., Adelsperger, J., Stone, R., Fabbro, D., Griffin, J.D., Gilliland, D.G. Blood (2005) [Pubmed]
  12. Fluorouracil selectively spares acute myeloid leukemia cells with long-term growth abilities in immunodeficient mice and in culture. Terpstra, W., Ploemacher, R.E., Prins, A., van Lom, K., Pouwels, K., Wognum, A.W., Wagemaker, G., Löwenberg, B., Wielenga, J.J. Blood (1996) [Pubmed]
  13. Survival of acute myeloid leukemia cells requires PI3 kinase activation. Xu, Q., Simpson, S.E., Scialla, T.J., Bagg, A., Carroll, M. Blood (2003) [Pubmed]
  14. Towards combination target-directed chemotherapy for chronic myeloid leukemia: role of farnesyl transferase inhibitors. Daley, G.Q. Semin. Hematol. (2003) [Pubmed]
  15. Role of RUNX1 in adult hematopoiesis: analysis of RUNX1-IRES-GFP knock-in mice reveals differential lineage expression. Lorsbach, R.B., Moore, J., Ang, S.O., Sun, W., Lenny, N., Downing, J.R. Blood (2004) [Pubmed]
  16. Involvement of Runx1 in the down-regulation of fetal liver kinase-1 expression during transition of endothelial cells to hematopoietic cells. Hirai, H., Samokhvalov, I.M., Fujimoto, T., Nishikawa, S., Imanishi, J., Nishikawa, S. Blood (2005) [Pubmed]
  17. AML1/Runx1 recruits calcineurin to regulate granulocyte macrophage colony-stimulating factor by Ets1 activation. Liu, H., Holm, M., Xie, X.Q., Wolf-Watz, M., Grundström, T. J. Biol. Chem. (2004) [Pubmed]
  18. The AML1-MTG8 leukemic fusion protein forms a complex with a novel member of the MTG8(ETO/CDR) family, MTGR1. Kitabayashi, I., Ida, K., Morohoshi, F., Yokoyama, A., Mitsuhashi, N., Shimizu, K., Nomura, N., Hayashi, Y., Ohki, M. Mol. Cell. Biol. (1998) [Pubmed]
  19. An activated receptor tyrosine kinase, TEL/PDGFbetaR, cooperates with AML1/ETO to induce acute myeloid leukemia in mice. Grisolano, J.L., O'Neal, J., Cain, J., Tomasson, M.H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  20. ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain. Amann, J.M., Nip, J., Strom, D.K., Lutterbach, B., Harada, H., Lenny, N., Downing, J.R., Meyers, S., Hiebert, S.W. Mol. Cell. Biol. (2001) [Pubmed]
  21. Positive and negative regulation of granulocyte-macrophage colony-stimulating factor promoter activity by AML1-related transcription factor, PEBP2. Takahashi, A., Satake, M., Yamaguchi-Iwai, Y., Bae, S.C., Lu, J., Maruyama, M., Zhang, Y.W., Oka, H., Arai, N., Arai, K. Blood (1995) [Pubmed]
  22. Constitutive activation of SHP2 in mice cooperates with ICSBP deficiency to accelerate progression to acute myeloid leukemia. Konieczna, I., Horvath, E., Wang, H., Lindsey, S., Saberwal, G., Bei, L., Huang, W., Platanias, L., Eklund, E.A. J. Clin. Invest. (2008) [Pubmed]
  23. Runx1 promotes angiogenesis by downregulation of insulin-like growth factor-binding protein-3. Iwatsuki, K., Tanaka, K., Kaneko, T., Kazama, R., Okamoto, S., Nakayama, Y., Ito, Y., Satake, M., Takahashi, S., Miyajima, A., Watanabe, T., Hara, T. Oncogene (2005) [Pubmed]
  24. Cbf beta is involved in maturation of all lineages of hematopoietic cells during embryogenesis except erythroid. Kundu, M., Liu, P.P. Blood Cells Mol. Dis. (2003) [Pubmed]
  25. Molecular basis of the t(8;21) translocation in acute myeloid leukaemia. Ohki, M. Semin. Cancer Biol. (1993) [Pubmed]
  26. Expression of Runx1, -2 and -3 during tooth, palate and craniofacial bone development. Yamashiro, T., Aberg, T., Levanon, D., Groner, Y., Thesleff, I. Gene Expr. Patterns (2002) [Pubmed]
  27. The osteoblast transcription factor Runx2 is expressed in mammary epithelial cells and mediates osteopontin expression. Inman, C.K., Shore, P. J. Biol. Chem. (2003) [Pubmed]
  28. Mechanisms of transcriptional repression by the t(8;21)-, t(12;21)-, and inv(16)-encoded fusion proteins. Heibert, S.W., Lutterbach, B., Durst, K., Wang, L., Linggi, B., Wu, S., Wood, L., Amann, J., King, D., Hou, Y. Cancer Chemother. Pharmacol. (2001) [Pubmed]
  29. Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Maier, H., Ostraat, R., Gao, H., Fields, S., Shinton, S.A., Medina, K.L., Ikawa, T., Murre, C., Singh, H., Hardy, R.R., Hagman, J. Nat. Immunol. (2004) [Pubmed]
  30. The core-binding factor leukemias: lessons learned from murine models. Downing, J.R. Curr. Opin. Genet. Dev. (2003) [Pubmed]
  31. Localization of the domains in Runx transcription factors required for the repression of CD4 in thymocytes. Telfer, J.C., Hedblom, E.E., Anderson, M.K., Laurent, M.N., Rothenberg, E.V. J. Immunol. (2004) [Pubmed]
  32. Overlapping expression of Runx1(Cbfa2) and Runx2(Cbfa1) transcription factors supports cooperative induction of skeletal development. Smith, N., Dong, Y., Lian, J.B., Pratap, J., Kingsley, P.D., van Wijnen, A.J., Stein, J.L., Schwarz, E.M., O'Keefe, R.J., Stein, G.S., Drissi, M.H. J. Cell. Physiol. (2005) [Pubmed]
  33. Crystallization and preliminary studies of the DNA-binding runt domain of AML1. Bäckström, S., Huang, S.H., Wolf-Watz, M., Xie, X.Q., Härd , T., Grundström, T., Sauer, U.H. Acta Crystallogr. D Biol. Crystallogr. (2001) [Pubmed]
  34. The transcriptionally active form of AML1 is required for hematopoietic rescue of the AML1-deficient embryonic para-aortic splanchnopleural (P-Sp) region. Goyama, S., Yamaguchi, Y., Imai, Y., Kawazu, M., Nakagawa, M., Asai, T., Kumano, K., Mitani, K., Ogawa, S., Chiba, S., Kurokawa, M., Hirai, H. Blood (2004) [Pubmed]
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