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Gene Review

Elf1  -  E74-like factor 1

Mus musculus

Synonyms: ETS-related transcription factor Elf-1, Elf-1, Sts1, mElf-1, p70
 
 
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Disease relevance of Elf1

 

High impact information on Elf1

  • T cells from mice lacking Sts-1 and Sts-2 are hyperresponsive to TCR stimulation [1].
  • In addition, by introducing mutations into the core of the site III Ets-like motif and comparing the corresponding effects on the in vitro binding of Elf-1 and the in vivo IL-2rE activity, we provide strong evidence that Elf-1 is directly involved in IL-2 responsiveness [2].
  • Elf-1 contributes to the function of the complex interleukin (IL)-2-responsive enhancer in the mouse IL-2 receptor alpha gene [2].
  • The nature of the functional cooperativity observed between Elf-1 and the factors binding sites I and II remains unresolved; experiments presented here however suggest that this effect may not require direct interactions between the proteins binding these three elements [2].
  • We have identified three critical motifs, which are essential for enhancer function and bind GATA-2, Fli-1 and Elf-1 in vivo [3].
 

Biological context of Elf1

 

Anatomical context of Elf1

  • We examined mElf-1 mRNA expression in normal mouse tissues and in several murine and human cell lines [8].
  • Subsequent molecular analysis demonstrated that both the -8 enhancer and the promoter depend on conserved Ets sites, which were bound in endothelial cells in vivo by Fli-1, Erg, and Elf-1 [9].
  • These results led to the identification of a bifunctional 5' enhancer (-3.8 element), which targets expression to hematopoietic progenitors and endothelium, contains conserved critical Ets sites, and is bound by Ets family transcription factors, including Fli-1 and Elf-1 [4].
  • Furthermore, we found that gene disruption of Elf-1 resulted in decreased CD1D1 expression on B cells but not other cell types, whereas conditional activation of PU.1 negatively regulated CD1D1 expression in PU.1-deficient myeloid cells [10].
  • Somewhat surprisingly, however, Elf-1 is also expressed at high levels in epithelial cells lining the oral cavity, the lung, the CNS, and the gastrointestinal and urinary tracts as well as in the skin of the developing mouse embryo and at lower levels in the adult mouse testis and liver [7].
 

Associations of Elf1 with chemical compounds

 

Other interactions of Elf1

  • Herein, we describe two related proteins, Sts-1 and Sts-2, that negatively regulate TCR signaling [1].
  • Here we demonstrate that Elf-1, an Ets-like protein, binds to site III and participates in IL-2 responsiveness [2].
  • Results obtained from the binding competition assay, nevertheless, suggest that NF-P1 and NF-P2 are related to but distinct from Ets proteins, e.g., Ets-1, Ets-2, and NF-AT/Elf-1, known to be expressed in T cells [14].
  • Mutation of the PU.1/Elf-1 site or the 3' site (FP4-3') within the context of the c-fes promoter resulted in substantially reduced activity in transient transfections [15].
  • Crystallization and initial crystal characterization of the C-terminal phosphoglycerate mutase homology domain of Sts-1 [13].
 

Analytical, diagnostic and therapeutic context of Elf1

References

  1. Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2. Carpino, N., Turner, S., Mekala, D., Takahashi, Y., Zang, H., Geiger, T.L., Doherty, P., Ihle, J.N. Immunity (2004) [Pubmed]
  2. Elf-1 contributes to the function of the complex interleukin (IL)-2-responsive enhancer in the mouse IL-2 receptor alpha gene. Serdobova, I., Pla, M., Reichenbach, P., Sperisen, P., Ghysdael, J., Wilson, A., Freeman, J., Nabholz, M. J. Exp. Med. (1997) [Pubmed]
  3. Establishing the transcriptional programme for blood: the SCL stem cell enhancer is regulated by a multiprotein complex containing Ets and GATA factors. Göttgens, B., Nastos, A., Kinston, S., Piltz, S., Delabesse, E.C., Stanley, M., Sanchez, M.J., Ciau-Uitz, A., Patient, R., Green, A.R. EMBO J. (2002) [Pubmed]
  4. The scl +18/19 stem cell enhancer is not required for hematopoiesis: identification of a 5' bifunctional hematopoietic-endothelial enhancer bound by Fli-1 and Elf-1. Göttgens, B., Broccardo, C., Sanchez, M.J., Deveaux, S., Murphy, G., Göthert, J.R., Kotsopoulou, E., Kinston, S., Delaney, L., Piltz, S., Barton, L.M., Knezevic, K., Erber, W.N., Begley, C.G., Frampton, J., Green, A.R. Mol. Cell. Biol. (2004) [Pubmed]
  5. Identification of ETS domain proteins in murine T lymphocytes that interact with the Moloney murine leukemia virus enhancer. Gunther, C.V., Graves, B.J. Mol. Cell. Biol. (1994) [Pubmed]
  6. Suppressors of T-cell receptor signaling Sts-1 and Sts-2 bind to Cbl and inhibit endocytosis of receptor tyrosine kinases. Kowanetz, K., Crosetto, N., Haglund, K., Schmidt, M.H., Heldin, C.H., Dikic, I. J. Biol. Chem. (2004) [Pubmed]
  7. Expression pattern of the Ets-related transcription factor Elf-1. Bassuk, A.G., Barton, K.P., Anandappa, R.T., Lu, M.M., Leiden, J.M. Mol. Med. (1998) [Pubmed]
  8. Cloning and expression of the murine Elf-1 cDNA. Davis, J.N., Roussel, M.F. Gene (1996) [Pubmed]
  9. Endoglin expression in the endothelium is regulated by Fli-1, Erg, and Elf-1 acting on the promoter and a -8-kb enhancer. Pimanda, J.E., Chan, W.Y., Donaldson, I.J., Bowen, M., Green, A.R., Göttgens, B. Blood (2006) [Pubmed]
  10. Transcriptional regulation of CD1D1 by Ets family transcription factors. Geng, Y., Laslo, P., Barton, K., Wang, C.R. J. Immunol. (2005) [Pubmed]
  11. Identification of elf1, a beta-spectrin, in early mouse liver development. Mishra, L., Cai, T., Levine, A., Weng, D., Mezey, E., Mishra, B., Gearhart, J. Int. J. Dev. Biol. (1998) [Pubmed]
  12. Differential effects of cyclic adenosine 3',5'-monophosphate on p70 ribosomal S6 kinase. Cass, L.A., Meinkoth, J.L. Endocrinology (1998) [Pubmed]
  13. Crystallization and initial crystal characterization of the C-terminal phosphoglycerate mutase homology domain of Sts-1. Kleinman, H., Ford, B., Keller, J., Carpino, N., Nassar, N. Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. (2006) [Pubmed]
  14. Identification of a killer cell-specific regulatory element of the mouse perforin gene: an Ets-binding site-homologous motif that interacts with Ets-related proteins. Koizumi, H., Horta, M.F., Youn, B.S., Fu, K.C., Kwon, B.S., Young, J.D., Liu, C.C. Mol. Cell. Biol. (1993) [Pubmed]
  15. The myeloid-cell-specific c-fes promoter is regulated by Sp1, PU.1, and a novel transcription factor. Heydemann, A., Juang, G., Hennessy, K., Parmacek, M.S., Simon, M.C. Mol. Cell. Biol. (1996) [Pubmed]
 
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