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Gene Review

MEIS1  -  Meis homeobox 1

Homo sapiens

Synonyms: Homeobox protein Meis1
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Disease relevance of MEIS1


Psychiatry related information on MEIS1

  • Although further psychometric analysis of the MEIS is warranted, the authors found that overall emotional intelligence, emotional perception, and emotional regulation uniquely explained individual cognitive-based performance over and beyond the level attributable to general intelligence [6].

High impact information on MEIS1

  • These and other studies showing that Meis1 is expressed at high levels in hematopoietic stem cells (HSCs) suggest that Meis1 may also be required for the proliferation/self-renewal of the HSC [7].
  • 5. In addition, Meis1-deficient embryos lack well-formed capillaries, although larger blood vessels are normal [7].
  • Likewise, in murine myeloid leukemia, transcriptional coactivation of Meis1 with HoxA7/A9 suggests that Meis1-HoxA7/9 heterodimers may evoke aberrant gene transcription [8].
  • Interestingly, while the Hoxa9 N-terminal domain (NTD) is essential for cooperative transformation with wild-type Meis1, it was dispensable in Vp16-Meis1 progenitors [9].
  • Surprisingly, Vp16-Meis1 (but not engrailed-Meis1) functioned as an autonomous oncoprotein that mimicked combined activities of Meis1 plus Hoxa9, immortalizing early progenitors, inducing low-level expression of Meis1-related signature genes, and causing leukemia without coexpression of exogenous or endogenous Hox genes [9].

Biological context of MEIS1


Anatomical context of MEIS1

  • HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells [1].
  • Most distinct was the correlation between MLL status and MEIS1 expression in ALL-derived cell lines: 8/8 MLLmu but 0/10 MLLwt cell lines expressed MEIS1 [13].
  • Here we demonstrate the expression of Pbx and Meis family cofactors in the human endometrium and their interaction with HOXA10 [12].
  • Immunohistochemical staining of selected AML samples showed moderate to high levels of HOXA9 protein, primarily cytoplasmic, in leukemic myeloblasts, with weaker and primarily nuclear staining for MEIS1 [4].
  • We also showed that MEIS1 can efficiently induce their conversion to leukemic stem cells, thus providing a novel model for the study of leukemic progression [14].

Associations of MEIS1 with chemical compounds

  • Subsequent to TSA treatment, MEIS1 recruitment lagged behind that of HOX and PBX partners [11].
  • We have previously demonstrated that homeodomain proteins, MEIS1 and PBXs, transactivate the PF4 gene through the novel regulatory element termed TME [15].
  • RA promotes proximalization of limb cells and endogenous RA signaling is required to maintain the proximal Meis domain in the limb [16].
  • This is the first example of a transcription factor oncoprotein (Meis1) that establishes expression of a tyrosine kinase oncoprotein (FLT3), and explains their coexpression in human leukemia [17].
  • At this concentration of dimethylsulfoxide, soluble F1 also catalyzes the spontaneous synthesis of a tightly bound ATP to a level of approximately 0.15 mol per mol F1 [Gómez-Puyou, A., Tuena de Gómez-Puyou, M. & de Meis, L. (1986) Eur. J. Biochem. 159, 133-140] [18].

Physical interactions of MEIS1

  • Previous studies have demonstrated that HOX-9 and HOX-10 paralog proteins are unique among HOX homeodomain proteins in their capacity to form in vitro cooperative DNA binding complexes with either the PBX or MEIS protein [1].
  • (iii) Although MEIS does not cooperatively bind DNA with ANTP class HOX proteins, it does form a trimer as a non-DNA-binding partner with DNA-bound PBX-HOXD4 [19].
  • Here we show that specific members of both PBX and MEIS subclasses form a multimeric complex with the pancreatic homeodomain protein PDX1 and switch the nature of its transcriptional activity [20].
  • Functional studies showed that PBX3C and PBX3D proteins were unable to interact with the PBX-interacting factor PREP1 and weakly interacted with MEIS proteins [21].
  • Here we show that PBX and Meis homeoproteins cooperatively bind the PBX-responsive sequence in vitro with the oncoprotein encoded by the non-clustered homeobox gene HOX11 activated by the t(10;14)(q24;q11) chromosomal translocation in T-cell acute lymphoblastic leukemia (T-ALL) [22].

Regulatory relationships of MEIS1

  • MEIS1 enhances in vitro HOXA9-PBX protein complex formation in the absence of DNA and forms a trimeric electrophoretic mobility shift assay (EMSA) complex with these proteins on an oligonucleotide containing a PBX-HOXA9 site [1].
  • A total of 89.5% of patients expressing MEIS1 co-expressed HOXA7 [23].
  • These observations suggest that association with PBX and MEIS partners controls the nature of the transcriptional activity of the organ-specific PDX1 transcription factor in exocrine versus endocrine cells [20].
  • These results indicate that PBX-MEIS1 complexes interact with nuclear T3 receptors to enhance T3 regulation of malic enzyme transcription in hepatocytes [24].

Other interactions of MEIS1


Analytical, diagnostic and therapeutic context of MEIS1


  1. HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells. Shen, W.F., Rozenfeld, S., Kwong, A., Köm ves, L.G., Lawrence, H.J., Largman, C. Mol. Cell. Biol. (1999) [Pubmed]
  2. Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice. Moskow, J.J., Bullrich, F., Huebner, K., Daar, I.O., Buchberg, A.M. Mol. Cell. Biol. (1995) [Pubmed]
  3. CALM-AF10+ T-ALL expression profiles are characterized by overexpression of HOXA and BMI1 oncogenes. Dik, W.A., Brahim, W., Braun, C., Asnafi, V., Dastugue, N., Bernard, O.A., van Dongen, J.J., Langerak, A.W., Macintyre, E.A., Delabesse, E. Leukemia (2005) [Pubmed]
  4. Frequent co-expression of the HOXA9 and MEIS1 homeobox genes in human myeloid leukemias. Lawrence, H.J., Rozenfeld, S., Cruz, C., Matsukuma, K., Kwong, A., Kömüves, L., Buchberg, A.M., Largman, C. Leukemia (1999) [Pubmed]
  5. The MEIS1 oncogene is highly expressed in neuroblastoma and amplified in cell line IMR32. Spieker, N., van Sluis, P., Beitsma, M., Boon, K., van Schaik, B.D., van Kampen, A.H., Caron, H., Versteeg, R. Genomics (2001) [Pubmed]
  6. Is emotional intelligence an advantage? An exploration of the impact of emotional and general intelligence on individual performance. Lam, L.T., Kirby, S.L. The Journal of social psychology. (2002) [Pubmed]
  7. Hematopoietic, angiogenic and eye defects in Meis1 mutant animals. Hisa, T., Spence, S.E., Rachel, R.A., Fujita, M., Nakamura, T., Ward, J.M., Devor-Henneman, D.E., Saiki, Y., Kutsuna, H., Tessarollo, L., Jenkins, N.A., Copeland, N.G. EMBO J. (2004) [Pubmed]
  8. Meis1 and pKnox1 bind DNA cooperatively with Pbx1 utilizing an interaction surface disrupted in oncoprotein E2a-Pbx1. Knoepfler, P.S., Calvo, K.R., Chen, H., Antonarakis, S.E., Kamps, M.P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  9. Persistent transactivation by meis1 replaces hox function in myeloid leukemogenesis models: evidence for co-occupancy of meis1-pbx and hox-pbx complexes on promoters of leukemia-associated genes. Wang, G.G., Pasillas, M.P., Kamps, M.P. Mol. Cell. Biol. (2006) [Pubmed]
  10. Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 gene. Okada, Y., Nagai, R., Sato, T., Matsuura, E., Minami, T., Morita, I., Doi, T. Blood (2003) [Pubmed]
  11. MEIS C termini harbor transcriptional activation domains that respond to cell signaling. Huang, H., Rastegar, M., Bodner, C., Goh, S.L., Rambaldi, I., Featherstone, M. J. Biol. Chem. (2005) [Pubmed]
  12. HOXA10, Pbx2, and Meis1 protein expression in the human endometrium: formation of multimeric complexes on HOXA10 target genes. Sarno, J.L., Kliman, H.J., Taylor, H.S. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  13. Expression of HOX genes in acute leukemia cell lines with and without MLL translocations. Quentmeier, H., Dirks, W.G., Macleod, R.A., Reinhardt, J., Zaborski, M., Drexler, H.G. Leuk. Lymphoma (2004) [Pubmed]
  14. Hox genes: from leukemia to hematopoietic stem cell expansion. Abramovich, C., Pineault, N., Ohta, H., Humphries, R.K. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  15. PREP1, MEIS1 homolog protein, regulates PF4 gene expression. Okada, Y., Matsuura, E., Nagai, R., Sato, T., Watanabe, A., Morita, I., Doi, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  16. Opposing RA and FGF signals control proximodistal vertebrate limb development through regulation of Meis genes. Mercader, N., Leonardo, E., Piedra, M.E., Martínez-A, C., Ros, M.A., Torres, M. Development (2000) [Pubmed]
  17. Meis1 programs transcription of FLT3 and cancer stem cell character, using a mechanism that requires interaction with Pbx and a novel function of the Meis1 C-terminus. Wang, G.G., Pasillas, M.P., Kamps, M.P. Blood (2005) [Pubmed]
  18. Synthesis and hydrolysis of ATP and the phosphate-ATP exchange reaction in soluble mitochondrial F1 in the presence of dimethylsulfoxide. Tuena de Gómez-Puyou, M., Pérez-Hernández, G., Gómez-Puyou, A. Eur. J. Biochem. (1999) [Pubmed]
  19. PBX and MEIS as non-DNA-binding partners in trimeric complexes with HOX proteins. Shanmugam, K., Green, N.C., Rambaldi, I., Saragovi, H.U., Featherstone, M.S. Mol. Cell. Biol. (1999) [Pubmed]
  20. An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 (MEIS2). Swift, G.H., Liu, Y., Rose, S.D., Bischof, L.J., Steelman, S., Buchberg, A.M., Wright, C.V., MacDonald, R.J. Mol. Cell. Biol. (1998) [Pubmed]
  21. Novel alternative PBX3 isoforms in leukemia cells with distinct interaction specificities. Milech, N., Kees, U.R., Watt, P.M. Genes Chromosomes Cancer (2001) [Pubmed]
  22. TALE homeoproteins as HOX11-interacting partners in T-cell leukemia. Allen, T.D., Zhu, Y.X., Hawley, T.S., Hawley, R.G. Leuk. Lymphoma (2000) [Pubmed]
  23. MEIS1 and HOXA7 genes in human acute myeloid leukemia. Afonja, O., Smith, J.E., Cheng, D.M., Goldenberg, A.S., Amorosi, E., Shimamoto, T., Nakamura, S., Ohyashiki, K., Ohyashiki, J., Toyama, K., Takeshita, K. Leuk. Res. (2000) [Pubmed]
  24. The homeodomain proteins PBX and MEIS1 are accessory factors that enhance thyroid hormone regulation of the malic enzyme gene in hepatocytes. Wang, Y., Yin, L., Hillgartner, F.B. J. Biol. Chem. (2001) [Pubmed]
  25. Multiple imprinted and stemness genes provide a link between normal and tumor progenitor cells of the developing human kidney. Dekel, B., Metsuyanim, S., Schmidt-Ott, K.M., Fridman, E., Jacob-Hirsch, J., Simon, A., Pinthus, J., Mor, Y., Barasch, J., Amariglio, N., Reisner, Y., Kaminski, N., Rechavi, G. Cancer Res. (2006) [Pubmed]
  26. The role of the MEIS homeobox genes in neuroblastoma. Geerts, D., Schilderink, N., Jorritsma, G., Versteeg, R. Cancer Lett. (2003) [Pubmed]
  27. Altered HOX gene expression in human skin and breast cancer cells. Svingen, T., Tonissen, K.F. Cancer Biol. Ther. (2003) [Pubmed]
  28. Molecular dissection of Meis1 reveals 2 domains required for leukemia induction and a key role for Hoxa gene activation. Mamo, A., Krosl, J., Kroon, E., Bijl, J., Thompson, A., Mayotte, N., Girard, S., Bisaillon, R., Beslu, N., Featherstone, M., Sauvageau, G. Blood (2006) [Pubmed]
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