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Gene Review

ELF4  -  E74-like factor 4 (ets domain...

Homo sapiens

Synonyms: E74-like factor 4, ELFR, ETS-related transcription factor Elf-4, MEF, Myeloid Elf-1-like factor
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Disease relevance of ELF4

  • ELF4 is fused to ERG in a case of acute myeloid leukemia with a t(X;21)(q25-26;q22) [1].
  • Arildone, a novel antiviral agent which blocks virion uncoating, was assessed for its ability to prevent paralysis and death in mice infected intracerebrally with a lethal dose of human poliovirus type-2 (strain MEF) [2].
  • Here we show that MEF is modified by conjugation with SUMO-1/-2 (small ubiquitin-related modifier) both in mammalian cells and in Escherichia coli overexpressing human SUMO-1/-2 [3].
  • RESULTS: Seropositivity rates and geometric mean titers (GMTs) for the Mahoney (type 1), MEF (type 2), and Saukett (type 3) poliovirus strains and the wild poliovirus type 1 strain were 99.3% (GMT--233.8), 98.6% (GMT--268.5), 99.3% (GMT--89.4), and 99.3% (GMT--139.5), respectively [4].
  • Interestingly, antibody to a synthetic peptide of PV-1 capsid protein VP2 exhibited IIA activity against PV-2 strain MEF [5].

High impact information on ELF4

  • From the embryo of this mouse, we prepared fibroblast cell lines, MEF-hC3G [6].
  • The Cre-expressing MEF-hC3G showed impaired cell adhesion, delayed cell spreading and accelerated cell migration [6].
  • We have previously shown that cyclin A-dependent phosphorylation of MEF largely restricts its activity to the G(1) phase of the cell cycle; we now show that MEF is a short-lived protein whose expression level also peaks during late G(1) phase [7].
  • Overexpression of MEF drives cells through the G(1)/S transition, thereby promoting cell proliferation [7].
  • MEF is an ETS-related transcription factor with strong transcriptional activating activity that affects hematopoietic stem cell behavior and is required for normal NK cell and NK T-cell development [7].

Chemical compound and disease context of ELF4

  • Fifty-four ears with evidence of pneumococcus (Pn) in the first acute otitis media (AOM) in 38 infants and with prolongation or recurrence of the MEF during the follow-up were observed for 7-22 months for the presence of Pn by culture or of pneumococcal antigen (Pn-ag) by counterimmunoelectrophoresis or latex agglutination methods in their MEFs [8].

Biological context of ELF4


Anatomical context of ELF4


Associations of ELF4 with chemical compounds

  • Here, we demonstrate that KLF6 protein is rapidly degraded when apoptosis is induced via the intrinsic pathway by cisplatin, adriamycin, or UVB irradiation in multiple cell lines (HCT116, SW40, HepG2, PC3-M, Skov3, NIH-3T3, 293T, GM09706, and MEF, IMR-90) [12].
  • We identified by point mutation that lysine 657 of MEF is the site for sumoylation [3].
  • Compared to saline, isoproterenol was followed by significantly increased FEV1 and MEF values (P less than 0.05) at both 10 and 30 minutes after medication, indicating reduction in bronchoconstriction [13].
  • After atenolol there was a decrease of FEV1 and MEF 50 at 5 h [14].
  • Metoprolol caused an increase in resistance at 2 and 5 h and a fall in FEV1, VC, and MEF 50 at 2 and 5 h [14].

Regulatory relationships of ELF4

  • In addition, heat-shock treatment induced the accumulation of MEF in endogenous PML nuclear bodies and enhanced MEF transactivation of lysozyme gene [9].
  • Furthermore, IL-8 mRNA expression in vitro was significantly down-regulated in MEF-overexpressing cells, compared with A549 cells [11].
  • Thus, our data indicate that MEF may play an important role in regulating HBD2 expression in epithelial cells [15].
  • MEF contains a central ETS domain and is expressed in a variety of myeloid leukemia cell lines and in normal adult hematopoietic tissue such as spleen, thymus and peripheral blood, as well as non-hematopoietic tissue such as ovary, placenta and colon [16].

Other interactions of ELF4

  • Thus, the recruitment of MEF to PML nuclear bodies may partly regulate lysozyme transcription in epithelial cells [9].
  • These data demonstrates that MEF is an important regulator of IL-8 expression [10].
  • Here, we show that PML stimulated MEF transcriptional activity, resulting in the up-regulation of endogenous HBD 2 expression [17].
  • The relative expression (RE) of MEF, but not ELF-1, was significantly lower (P<0.0001) in AML with t(8;21) and t(15;17) compared with AML with normal karyotype [18].
  • MEF overexpression induced morphological changes, such as the conversion of normally loose cell-cell contacts to strong interactions similar to those seen in the presence of matrix metalloproteinase (MMP) inhibitor BB94 [11].

Analytical, diagnostic and therapeutic context of ELF4


  1. ELF4 is fused to ERG in a case of acute myeloid leukemia with a t(X;21)(q25-26;q22). Moore, S.D., Offor, O., Ferry, J.A., Amrein, P.C., Morton, C.C., Dal Cin, P. Leuk. Res. (2006) [Pubmed]
  2. Prevention of human poliovirus-induced paralysis and death in mice by the novel antiviral agent arildone. McKinlay, M.A., Miralles, J.V., Brisson, C.J., Pancic, F. Antimicrob. Agents Chemother. (1982) [Pubmed]
  3. SUMO down-regulates the activity of Elf4/myeloid Elf-1-like factor. Suico, M.A., Nakamura, H., Lu, Z., Saitoh, H., Shuto, T., Nakao, M., Kai, H. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  4. Immune status to poliovirus among immigrant workers in Israel. Calderon-Margalit, R., Sofer, D., Gefen, D., Lewis, M., Shulman, L., Mendelson, E., Swartz, T.A., Shohat, T. Preventive medicine. (2005) [Pubmed]
  5. An assay for the detection of interferon dependent and interferon independent antibody activities. Langford, M.P., Kaiwar, R. J. Virol. Methods (1990) [Pubmed]
  6. Requirement for C3G-dependent Rap1 activation for cell adhesion and embryogenesis. Ohba, Y., Ikuta, K., Ogura, A., Matsuda, J., Mochizuki, N., Nagashima, K., Kurokawa, K., Mayer, B.J., Maki, K., Miyazaki , J., Matsuda, M. EMBO J. (2001) [Pubmed]
  7. The ETS protein MEF is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCFSkp2. Liu, Y., Hedvat, C.V., Mao, S., Zhu, X.H., Yao, J., Nguyen, H., Koff, A., Nimer, S.D. Mol. Cell. Biol. (2006) [Pubmed]
  8. Pneumococcal bacteriology after pneumococcal otitis media with special reference to pneumococcal antigens. Karma, P., Sipilä, P., Virtanen, T., Luotonen, J., Sipilä, M., Häivä, V.M. Int. J. Pediatr. Otorhinolaryngol. (1985) [Pubmed]
  9. Myeloid Elf-1-like factor, an ETS transcription factor, up-regulates lysozyme transcription in epithelial cells through interaction with promyelocytic leukemia protein. Suico, M.A., Yoshida, H., Seki, Y., Uchikawa, T., Lu, Z., Shuto, T., Matsuzaki, K., Nakao, M., Li, J.D., Kai, H. J. Biol. Chem. (2004) [Pubmed]
  10. Myeloid ELF1-like factor is a potent activator of interleukin-8 expression in hematopoietic cells. Hedvat, C.V., Yao, J., Sokolic, R.A., Nimer, S.D. J. Biol. Chem. (2004) [Pubmed]
  11. The ETS transcription factor MEF is a candidate tumor suppressor gene on the X chromosome. Seki, Y., Suico, M.A., Uto, A., Hisatsune, A., Shuto, T., Isohama, Y., Kai, H. Cancer Res. (2002) [Pubmed]
  12. KLF6 degradation after apoptotic DNA damage. Banck, M.S., Beaven, S.W., Narla, G., Walsh, M.J., Friedman, S.L., Beutler, A.S. FEBS Lett. (2006) [Pubmed]
  13. The effect of glucagon on airway resistance. Imbruce, R., Goldfedder, A., Maguire, W., Briscoe, W., Nair, S. Journal of clinical pharmacology. (1975) [Pubmed]
  14. The effect of the cardioselective beta blocker celiprolol on pulmonary function in asthmatic patients. Schindl, R., Würtz, J., Hoffmann, H. J. Cardiovasc. Pharmacol. (1986) [Pubmed]
  15. MEF up-regulates human beta-defensin 2 expression in epithelial cells. Lu, Z., Kim, K.A., Suico, M.A., Shuto, T., Li, J.D., Kai, H. FEBS Lett. (2004) [Pubmed]
  16. MEF, a novel transcription factor with an Elf-1 like DNA binding domain but distinct transcriptional activating properties. Miyazaki, Y., Sun, X., Uchida, H., Zhang, J., Nimer, S. Oncogene (1996) [Pubmed]
  17. The regulation of human beta-defensin 2 by the ETS transcription factor MEF (myeloid Elf-1-like factor) is enhanced by promyelocytic leukemia protein. Suico, M.A., Lu, Z., Shuto, T., Koga, T., Uchikawa, T., Yoshida, H., Matsuzaki, K., Nakao, M., Li, J.D., Kai, H. J. Pharmacol. Sci. (2004) [Pubmed]
  18. The level of MEF but not ELF-1 correlates with FAB subtype of acute myeloid leukemia and is low in good prognosis cases. Fukushima, T., Miyazaki, Y., Tsushima, H., Tsutsumi, C., Taguchi, J., Yoshida, S., Kuriyama, K., Scadden, D., Nimer, S., Tomonaga, M. Leuk. Res. (2003) [Pubmed]
  19. Cloning of a novel human ELF-1-related ETS transcription factor, ELFR, its characterization and chromosomal assignment relative to ELF-1. Aryee, D.N., Petermann, R., Kos, K., Henn, T., Haas, O.A., Kovar, H. Gene (1998) [Pubmed]
  20. Functional dissection of the ETS transcription factor MEF. Suico, M.A., Koyanagi, T., Ise, S., Lu, Z., Hisatsune, A., Seki, Y., Shuto, T., Isohama, Y., Miyata, T., Kai, H. Biochim. Biophys. Acta (2002) [Pubmed]
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