The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

RUNX1  -  runt-related transcription factor 1

Homo sapiens

Synonyms: AML1, AML1-EVI-1, AMLCR1, Acute myeloid leukemia 1 protein, CBF-alpha-2, ...
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of RUNX1

 

Psychiatry related information on RUNX1

  • In this report, we showed that AML1 point mutations were found in 6 (46%) of 13 MDS patients among atomic bomb (A-bomb) survivors in Hiroshima. Unlike acute or chronic leukemia patients among A-bomb survivors, MDS patients exposed relatively low-dose radiation and developed the disease after a long latency period [6].
 

High impact information on RUNX1

 

Chemical compound and disease context of RUNX1

 

Biological context of RUNX1

  • Surprisingly, expression of the chromosome 21 gene RUNX1, a known regulator of megakaryopoiesis, was not elevated in DS-AMKL [13].
  • A unique subset of differentially expressed genes, outside the CRA and CRD, were identified when gene expression signatures of iAMP21 were compared to ALL samples with ETV6-RUNX1 fusion (n = 21) or high hyperdiploidy with additional chromosomes 21 (n = 23) [2].
  • Role of RUNX1 in adult hematopoiesis: analysis of RUNX1-IRES-GFP knock-in mice reveals differential lineage expression [14].
  • Functional investigations of the 7 FPD/AML RUNX1 Runt domain point mutations described to date (2 frameshift, 2 nonsense, and 3 missense mutations) were performed [15].
  • In general, missense and nonsense RUNX1 proteins retained the ability to heterodimerize with PEBP2beta/CBFbeta and inhibited transactivation of a reporter gene by wild-type RUNX1 [15].
 

Anatomical context of RUNX1

  • Immunostaining of healthy human bone marrow confirmed a strong expression of RUNX1 and its cofactor, core-binding factor beta (CBFbeta), in megakaryocytes and a minimal expression in erythroblasts [16].
  • Enforced RUNX1 expression in K562 cells enhanced the induction of the megakaryocytic integrin proteins alphaIIb and alpha2 [16].
  • During megakaryocytic induction in this system, the myeloid transcription factor RUNX1 underwent up-regulation, dependent on ERK signaling and inhibitable by stromal cell contact [16].
  • In this report, we demonstrate that MHC class I gene expression is enhanced by the T cell enhanceosome and results from a direct interaction of the RUNX1-containing complex with the class I gene in vivo [17].
  • Changes in RUNX1 activity affect endogenous protein kinase Cbeta expression, and a dominant-negative form of RUNX1 protects U937 cells from apoptotic stimuli previously shown to be dependent on protein kinase Cbeta [18].
 

Associations of RUNX1 with chemical compounds

  • The RUNX1 Runt domain at 1.25A resolution: a structural switch and specifically bound chloride ions modulate DNA binding [19].
  • Previously, we reported that AML1 is phosphorylated on two serine residues with dependence on activation of extracellular signal-regulated kinase, which positively regulates the transcriptional activity of AML1 [20].
  • Here we report the first crystal structure of an NMTS in an AML-1 segment fused to glutathione S-transferase [21].
  • These findings have established that TEL-AML1 ALL has significantly lower de novo purine synthesis and differential expression of genes involved in purine metabolism [9].
  • The protein product of AML1 deltaN lacks the N-terminal region of AML1, including half of the Runt domain, and neither binds to DNA nor heterodimerizes with the beta subunit [22].
  • Mutation to alanine increased DNA affinity, suggesting that in other gene or cellular contexts phosphorylation of RUNX1 by cdks may reduce transactivation [23].
  • PRMT1- dependent methylation of RUNX1 at these arginine residues abrogates its association with SIN3A, whereas shRNA against PRMT1 (or use of a methyltransferase inhibitor) enhances this association [24].
 

Physical interactions of RUNX1

  • Thus, we hypothesized that DNMT1 is also part of the transcriptional repressor complex recruited by RUNX1/MTG8 [4].
  • NERF-2 bound to AML1 via an interaction site located in a basic region upstream of the Ets domain [25].
  • Although CBFB forms a core-binding factor transcriptional complex with RUNX1, previous analyses have excluded the CBFB gene as the leukemia-predisposing gene in these families [26].
  • Runx1 binds the silencer and represses CD4 transcription in immature thymocytes [27].
  • Using gel-shift assay, we showed that AML1-ETO and AML1-MTG16 bound to a series of AML1 consensus DNA-binding sites with different affinities [28].
  • Promoter cytosine methylation analysis indicates that RUNX1/AML1 binds to rDNA repeats that are more highly CpG methylated than those bound by AML1-ETO [29].
 

Enzymatic interactions of RUNX1

 

Regulatory relationships of RUNX1

  • Knockdown of RUNX3 in these cells induces RUNX1 expression and inhibits cell proliferation, directly showing that RUNX proteins can regulate B-cell growth [32].
  • BACH1 was significantly overexpressed in fetal DS (p < 0.008) as compared to controls whereas RUNX1 and ERG proteins were comparable between groups, and SIM2 l was not detectable in any specimen [33].
  • We further demonstrate that MOZ can activate the MIP-1alpha promoter and that this activation is largely dependent upon the proximal RUNX site [34].
  • It appears that loss of TEL function activates a pathway that cooperates with TEL/RUNX1 and sequesters coactivator(s) into nonfunctional complex in the cytoplasm thus inhibiting transcription of target genes [35].
  • Recent studies have revealed the involvement of AML1 transactivation activity in promoting cell cycle progression through the induction of cyclin D proteins [36].
 

Other interactions of RUNX1

  • Our experiments provide for the first time a direct insight into the chromatin structure of an AML1-ETO-bound target gene [37].
  • Furthermore, the interaction of AML1 with CBFbeta is essential for haematopoiesis [38].
  • The AML1-ETO complex does not disrupt binding of other transcription factors, indicating that c-FMS is not irreversibly epigenetically silenced [37].
  • To study the origin of TEL-AML1-induced ALL, we generated transgenic zebrafish expressing TEL-AML1 either ubiquitously or in lymphoid progenitors [39].
  • Although the reciprocal chimeric product, MTG16-AML1, was also detected in one of the t(16;21) patients, its protein product was predicted to be truncated [40].
 

Analytical, diagnostic and therapeutic context of RUNX1

References

  1. A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis. Helms, C., Cao, L., Krueger, J.G., Wijsman, E.M., Chamian, F., Gordon, D., Heffernan, M., Daw, J.A., Robarge, J., Ott, J., Kwok, P.Y., Menter, A., Bowcock, A.M. Nat. Genet. (2003) [Pubmed]
  2. Complex genomic alterations and gene expression in acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21. Strefford, J.C., van Delft, F.W., Robinson, H.M., Worley, H., Yiannikouris, O., Selzer, R., Richmond, T., Hann, I., Bellotti, T., Raghavan, M., Young, B.D., Saha, V., Harrison, C.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. Genomic DNA breakpoints in AML1/RUNX1 and ETO cluster with topoisomerase II DNA cleavage and DNase I hypersensitive sites in t(8;21) leukemia. Zhang, Y., Strissel, P., Strick, R., Chen, J., Nucifora, G., Le Beau, M.M., Larson, R.A., Rowley, J.D. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  4. Interplay of RUNX1/MTG8 and DNA methyltransferase 1 in acute myeloid leukemia. Liu, S., Shen, T., Huynh, L., Klisovic, M.I., Rush, L.J., Ford, J.L., Yu, J., Becknell, B., Li, Y., Liu, C., Vukosavljevic, T., Whitman, S.P., Chang, K.S., Byrd, J.C., Perrotti, D., Plass, C., Marcucci, G. Cancer Res. (2005) [Pubmed]
  5. RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance. Roche-Lestienne, C., Deluche, L., Corm, S., Tigaud, I., Joha, S., Philippe, N., Geffroy, S., Laï, J.L., Nicolini, F.E., Preudhomme, C. Blood (2008) [Pubmed]
  6. Implications of somatic mutations in the AML1 gene in radiation-associated and therapy-related myelodysplastic syndrome/acute myeloid leukemia. Harada, H., Harada, Y., Tanaka, H., Kimura, A., Inaba, T. Blood (2003) [Pubmed]
  7. An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis. Tokuhiro, S., Yamada, R., Chang, X., Suzuki, A., Kochi, Y., Sawada, T., Suzuki, M., Nagasaki, M., Ohtsuki, M., Ono, M., Furukawa, H., Nagashima, M., Yoshino, S., Mabuchi, A., Sekine, A., Saito, S., Takahashi, A., Tsunoda, T., Nakamura, Y., Yamamoto, K. Nat. Genet. (2003) [Pubmed]
  8. A RUNX trio with a taste for autoimmunity. Alarcón-Riquelme, M.E. Nat. Genet. (2003) [Pubmed]
  9. Acute lymphoblastic leukemia with TEL-AML1 fusion has lower expression of genes involved in purine metabolism and lower de novo purine synthesis. Zaza, G., Yang, W., Kager, L., Cheok, M., Downing, J., Pui, C.H., Cheng, C., Relling, M.V., Evans, W.E. Blood (2004) [Pubmed]
  10. Analysis of RUNX1 binding site and RAPTOR polymorphisms in psoriasis: no evidence for association despite adequate power and evidence for linkage. Stuart, P., Nair, R.P., Abecasis, G.R., Nistor, I., Hiremagalore, R., Chia, N.V., Qin, Z.S., Thompson, R.A., Jenisch, S., Weichenthal, M., Janiga, J., Lim, H.W., Christophers, E., Voorhees, J.J., Elder, J.T. J. Med. Genet. (2006) [Pubmed]
  11. The association of the TEL-AML1 chromosomal translocation with the accumulation of methotrexate polyglutamates in lymphoblasts and with ploidy in childhood B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group study. Whitehead, V.M., Payment, C., Cooley, L., Lauer, S.J., Mahoney, D.H., Shuster, J.J., Vuchich, M.J., Bernstein, M.L., Look, A.T., Pullen, D.J., Camitta, B. Leukemia (2001) [Pubmed]
  12. Effect of the histone deacetylase inhibitor depsipeptide on B-cell differentiation in both TEL-AML1-positive and negative childhood acute lymphoblastic leukemia. Stams, W.A., den Boer, M.L., Beverloo, H.B., Kazemier, K.M., van Wering, E.R., Janka-Schaub, G.E., Pieters, R. Haematologica (2005) [Pubmed]
  13. Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling. Bourquin, J.P., Subramanian, A., Langebrake, C., Reinhardt, D., Bernard, O., Ballerini, P., Baruchel, A., Cavé, H., Dastugue, N., Hasle, H., Kaspers, G.L., Lessard, M., Michaux, L., Vyas, P., van Wering, E., Zwaan, C.M., Golub, T.R., Orkin, S.H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  14. 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]
  15. In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis. Michaud, J., Wu, F., Osato, M., Cottles, G.M., Yanagida, M., Asou, N., Shigesada, K., Ito, Y., Benson, K.F., Raskind, W.H., Rossier, C., Antonarakis, S.E., Israels, S., McNicol, A., Weiss, H., Horwitz, M., Scott, H.S. Blood (2002) [Pubmed]
  16. RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation. Elagib, K.E., Racke, F.K., Mogass, M., Khetawat, R., Delehanty, L.L., Goldfarb, A.N. Blood (2003) [Pubmed]
  17. A T lymphocyte-specific transcription complex containing RUNX1 activates MHC class I expression. Howcroft, T.K., Weissman, J.D., Gegonne, A., Singer, D.S. J. Immunol. (2005) [Pubmed]
  18. A chromatin immunoprecipitation screen reveals protein kinase Cbeta as a direct RUNX1 target gene. Hug, B.A., Ahmed, N., Robbins, J.A., Lazar, M.A. J. Biol. Chem. (2004) [Pubmed]
  19. The RUNX1 Runt domain at 1.25A resolution: a structural switch and specifically bound chloride ions modulate DNA binding. Bäckström, S., Wolf-Watz, M., Grundström, C., Härd, T., Grundström, T., Sauer, U.H. J. Mol. Biol. (2002) [Pubmed]
  20. The corepressor mSin3A regulates phosphorylation-induced activation, intranuclear location, and stability of AML1. Imai, Y., Kurokawa, M., Yamaguchi, Y., Izutsu, K., Nitta, E., Mitani, K., Satake, M., Noda, T., Ito, Y., Hirai, H. Mol. Cell. Biol. (2004) [Pubmed]
  21. Crystal structure of the nuclear matrix targeting signal of the transcription factor acute myelogenous leukemia-1/polyoma enhancer-binding protein 2alphaB/core binding factor alpha2. Tang, L., Guo, B., Javed, A., Choi, J.Y., Hiebert, S., Lian, J.B., van Wijnen, A.J., Stein, J.L., Stein, G.S., Zhou, G.W. J. Biol. Chem. (1999) [Pubmed]
  22. A novel transcript encoding an N-terminally truncated AML1/PEBP2 alphaB protein interferes with transactivation and blocks granulocytic differentiation of 32Dcl3 myeloid cells. Zhang, Y.W., Bae, S.C., Huang, G., Fu, Y.X., Lu, J., Ahn, M.Y., Kanno, Y., Kanno, T., Ito, Y. Mol. Cell. Biol. (1997) [Pubmed]
  23. Cyclin-dependent kinase phosphorylation of RUNX1/AML1 on 3 sites increases transactivation potency and stimulates cell proliferation. Zhang, L., Fried, F.B., Guo, H., Friedman, A.D. Blood (2008) [Pubmed]
  24. Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity. Zhao, X., Jankovic, V., Gural, A., Huang, G., Pardanani, A., Menendez, S., Zhang, J., Dunne, R., Xiao, A., Erdjument-Bromage, H., Allis, C.D., Tempst, P., Nimer, S.D. Genes Dev. (2008) [Pubmed]
  25. Isoforms of the Ets transcription factor NERF/ELF-2 physically interact with AML1 and mediate opposing effects on AML1-mediated transcription of the B cell-specific blk gene. Cho, J.Y., Akbarali, Y., Zerbini, L.F., Gu, X., Boltax, J., Wang, Y., Oettgen, P., Zhang, D.E., Libermann, T.A. J. Biol. Chem. (2004) [Pubmed]
  26. Chromosome band 16q22-linked familial AML: exclusion of candidate genes, and possible disease risk modification by NQO1 polymorphisms. Escher, R., Jones, A., Hagos, F., Carmichael, C., Horwitz, M., Olopade, O.I., Scott, H.S. Genes Chromosomes Cancer (2004) [Pubmed]
  27. Runx1 binds positive transcription elongation factor b and represses transcriptional elongation by RNA polymerase II: possible mechanism of CD4 silencing. Jiang, H., Zhang, F., Kurosu, T., Peterlin, B.M. Mol. Cell. Biol. (2005) [Pubmed]
  28. Decreased intranuclear mobility of acute myeloid leukemia 1-containing fusion proteins is accompanied by reduced mobility and compartmentalization of core binding factor beta. Qiu, J., Wong, J., Tweardy, D.J., Dong, S. Oncogene (2006) [Pubmed]
  29. The leukemogenic t(8;21) fusion protein AML1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes. Bakshi, R., Zaidi, S.K., Pande, S., Hassan, M.Q., Young, D.W., Montecino, M., Lian, J.B., van Wijnen, A.J., Stein, J.L., Stein, G.S. J. Cell. Sci. (2008) [Pubmed]
  30. Expression profile of wild-type ETV6 in childhood acute leukaemia. Patel, N., Goff, L.K., Clark, T., Ford, A.M., Foot, N., Lillington, D., Hing, S., Pritchard-Jones, K., Jones, L.K., Saha, V. Br. J. Haematol. (2003) [Pubmed]
  31. Intranuclear targeting of AML/CBFalpha regulatory factors to nuclear matrix-associated transcriptional domains. Zeng, C., McNeil, S., Pockwinse, S., Nickerson, J., Shopland, L., Lawrence, J.B., Penman, S., Hiebert, S., Lian, J.B., van Wijnen, A.J., Stein, J.L., Stein, G.S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  32. RUNX expression and function in human B cells. Whiteman, H.J., Farrell, P.J. Crit. Rev. Eukaryot. Gene Expr. (2006) [Pubmed]
  33. Overexpression of transcription factor BACH1 in fetal Down syndrome brain. Ferrando-Miguel, R., Cheon, M.S., Yang, J.W., Lubec, G. J. Neural Transm. Suppl. (2003) [Pubmed]
  34. Transcriptional regulation of the human MIP-1alpha promoter by RUNX1 and MOZ. Bristow, C.A., Shore, P. Nucleic Acids Res. (2003) [Pubmed]
  35. Mechanism of transcriptional repression by TEL/RUNX1 fusion protein. Lee, Y.J., Kim, J.H., Bae, S., Rho, S.K., Choe, S.Y. Mol. Cells (2004) [Pubmed]
  36. The hematopoietic transcription factor AML1 (RUNX1) is negatively regulated by the cell cycle protein cyclin D3. Peterson, L.F., Boyapati, A., Ranganathan, V., Iwama, A., Tenen, D.G., Tsai, S., Zhang, D.E. Mol. Cell. Biol. (2005) [Pubmed]
  37. Epigenetic consequences of AML1-ETO action at the human c-FMS locus. Follows, G.A., Tagoh, H., Lefevre, P., Hodge, D., Morgan, G.J., Bonifer, C. EMBO J. (2003) [Pubmed]
  38. Structural basis for the heterodimeric interaction between the acute leukaemia-associated transcription factors AML1 and CBFbeta. Warren, A.J., Bravo, J., Williams, R.L., Rabbitts, T.H. EMBO J. (2000) [Pubmed]
  39. TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia. Sabaawy, H.E., Azuma, M., Embree, L.J., Tsai, H.J., Starost, M.F., Hickstein, D.D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  40. The partner gene of AML1 in t(16;21) myeloid malignancies is a novel member of the MTG8(ETO) family. Gamou, T., Kitamura, E., Hosoda, F., Shimizu, K., Shinohara, K., Hayashi, Y., Nagase, T., Yokoyama, Y., Ohki, M. Blood (1998) [Pubmed]
  41. Identification of RUNX1/AML1 as a classical tumor suppressor gene. Silva, F.P., Morolli, B., Storlazzi, C.T., Anelli, L., Wessels, H., Bezrookove, V., Kluin-Nelemans, H.C., Giphart-Gassler, M. Oncogene (2003) [Pubmed]
  42. RUNX1 associates with histone deacetylases and SUV39H1 to repress transcription. Reed-Inderbitzin, E., Moreno-Miralles, I., Vanden-Eynden, S.K., Xie, J., Lutterbach, B., Durst-Goodwin, K.L., Luce, K.S., Irvin, B.J., Cleary, M.L., Brandt, S.J., Hiebert, S.W. Oncogene (2006) [Pubmed]
  43. Frequent downregulation of the runt domain transcription factors RUNX1, RUNX3 and their cofactor CBFB in gastric cancer. Sakakura, C., Hagiwara, A., Miyagawa, K., Nakashima, S., Yoshikawa, T., Kin, S., Nakase, Y., Ito, K., Yamagishi, H., Yazumi, S., Chiba, T., Ito, Y. Int. J. Cancer (2005) [Pubmed]
 
WikiGenes - Universities