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Gene Review

Egr3  -  early growth response 3

Mus musculus

Synonyms: EGR-3, Early growth response protein 3, Egr-3, Pilot
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Disease relevance of Egr3


High impact information on Egr3

  • Thus, transient induction of Egr3 delays the effects of RORgammat and enables pre-TCR signaling to induce both proliferation and gene rearrangement [3].
  • Conversely, T cells from Egr3(-/-) mice had lower expression of Cbl-b and were resistant to in vivo peptide-induced tolerance [4].
  • Egr-2 and Egr-3 are negative regulators of T cell activation [4].
  • Recent molecular studies have identified the gonadotropin subunit, luteinizing hormone beta, as an EGR1-regulated gene in vivo and uncovered an essential role for EGR3 in muscle-spindle development [5].
  • We have monitored the expression of three transcription factors, Egr3, Pea3, and Erm, that delineate early muscle spindle development in an assay of muscle spindle-inducing signals [6].

Biological context of Egr3

  • The transcription factor Egr3 modulates sensory axon-myotube interactions during muscle spindle morphogenesis [7].
  • In Egr3-deficient mice, myotubes received Ia afferent innervation and assembled normally into spindles during embryogenesis [7].
  • Egr3 is a transcriptional regulator that contains a zinc-finger DNA binding domain [8].
  • We have also generated transgenic mice that express high levels of Egr3 constitutively, and when these mice are bred onto a Rag1(-/-) background they exhibit increased proliferation in the absence of stimulation and have pre-TCR alpha-chain and CD25 down-regulation, as well as increased Calpha expression [8].
  • Constitutive transgenic expression of Egr3 in thymocytes increases apoptosis among DP cells and shortens their survival in vitro [9].

Anatomical context of Egr3

  • In wild type mice, Egr3 was expressed in developing myotubes shortly after they were innervated by Ia afferents and its expression was controlled by innervation because it dissipated following nerve transection [7].
  • As germ cells form longer interconnected chains (incomplete cytokinesis), the Egr3 signal disappears coincident with a loss of stem cell activity [10].

Associations of Egr3 with chemical compounds

  • Constitutive transgenic expression of Egr3 results in poor expression of Bcl-x(L) and the thymic isoform of retinoic acid receptor-related orphan receptor gamma (RORgammat) in DP thymocytes, two molecules that are required in DP cells for normal life span [9].
  • Cyclosporin A-sensitive transcription factor Egr-3 regulates Fas ligand expression [11].
  • Despite their sensitivity to this therapeutic effect of clozapine, Egr3-/- mice display a marked resistance to the sedating effects of acute clozapine compared with WT littermate controls [12].

Other interactions of Egr3

  • NAB1 also represses Krox20 activity, but it does not influence Egr3 or NGFI-G, thus providing a mechanism for the differential regulation of this family of immediate-early transcription factors [13].
  • Although overexpressed Egr-1 was ineffective, overexpressed Egr-2 was as potent as Egr-3 in inducing fasL promoter-dependent reporter constructs in T cell hybridomas and HeLa cells, and both up-regulated endogenous fasL mRNA in HeLa cells [14].
  • Moreover, slow-developmental myosin heavy chain was not induced in embryonic Egr3-deficient spindles suggesting that impairments in differentiation were present before they could be detected morphologically [7].
  • Ectopic expression of Egr-3 but not Sp1 protein in the abnormal DN T cells enhanced fasl promoter activity, suggesting that the Egr but not Sp1 was limiting for fasl gene activation [15].

Analytical, diagnostic and therapeutic context of Egr3


  1. Muscle spindle-derived neurotrophin 3 regulates synaptic connectivity between muscle sensory and motor neurons. Chen, H.H., Tourtellotte, W.G., Frank, E. J. Neurosci. (2002) [Pubmed]
  2. Abnormal sympathetic nervous system development and physiological dysautonomia in Egr3-deficient mice. Eldredge, L.C., Gao, X.M., Quach, D.H., Li, L., Han, X., Lomasney, J., Tourtellotte, W.G. Development (2008) [Pubmed]
  3. Interplay between RORgammat, Egr3, and E proteins controls proliferation in response to pre-TCR signals. Xi, H., Schwartz, R., Engel, I., Murre, C., Kersh, G.J. Immunity (2006) [Pubmed]
  4. Egr-2 and Egr-3 are negative regulators of T cell activation. Safford, M., Collins, S., Lutz, M.A., Allen, A., Huang, C.T., Kowalski, J., Blackford, A., Horton, M.R., Drake, C., Schwartz, R.H., Powell, J.D. Nat. Immunol. (2005) [Pubmed]
  5. The EGR family of transcription-regulatory factors: progress at the interface of molecular and systems neuroscience. O'Donovan, K.J., Tourtellotte, W.G., Millbrandt, J., Baraban, J.M. Trends Neurosci. (1999) [Pubmed]
  6. A role for neuregulin1 signaling in muscle spindle differentiation. Hippenmeyer, S., Shneider, N.A., Birchmeier, C., Burden, S.J., Jessell, T.M., Arber, S. Neuron (2002) [Pubmed]
  7. The transcription factor Egr3 modulates sensory axon-myotube interactions during muscle spindle morphogenesis. Tourtellotte, W.G., Keller-Peck, C., Milbrandt, J., Kucera, J. Dev. Biol. (2001) [Pubmed]
  8. Early growth response gene 3 regulates thymocyte proliferation during the transition from CD4-CD8- to CD4+CD8+. Xi, H., Kersh, G.J. J. Immunol. (2004) [Pubmed]
  9. Sustained early growth response gene 3 expression inhibits the survival of CD4/CD8 double-positive thymocytes. Xi, H., Kersh, G.J. J. Immunol. (2004) [Pubmed]
  10. Defining the spermatogonial stem cell. Hamra, F.K., Schultz, N., Chapman, K.M., Grellhesl, D.M., Cronkhite, J.T., Hammer, R.E., Garbers, D.L. Dev. Biol. (2004) [Pubmed]
  11. Cyclosporin A-sensitive transcription factor Egr-3 regulates Fas ligand expression. Mittelstadt, P.R., Ashwell, J.D. Mol. Cell. Biol. (1998) [Pubmed]
  12. Mice lacking the immediate early gene Egr3 respond to the anti-aggressive effects of clozapine yet are relatively resistant to its sedating effects. Gallitano-Mendel, A., Wozniak, D.F., Pehek, E.A., Milbrandt, J. Neuropsychopharmacology (2008) [Pubmed]
  13. Identification of NAB1, a repressor of NGFI-A- and Krox20-mediated transcription. Russo, M.W., Sevetson, B.R., Milbrandt, J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  14. Role of Egr-2 in up-regulation of Fas ligand in normal T cells and aberrant double-negative lpr and gld T cells. Mittelstadt, P.R., Ashwell, J.D. J. Biol. Chem. (1999) [Pubmed]
  15. Sp1 is the major fasl gene activator in abnormal CD4(-)CD8(-)B220(+) T cells of lpr and gld mice. Xiao, S., Marshak-Rothstein, A., Ju, S.T. Eur. J. Immunol. (2001) [Pubmed]
  16. Early growth response-1 is required for CD154 transcription. Cron, R.Q., Bandyopadhyay, R., Genin, A., Brunner, M., Kersh, G.J., Yin, J., Finkel, T.H., Crow, M.K. J. Immunol. (2006) [Pubmed]
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