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Gene Review

Egr3  -  early growth response 3

Rattus norvegicus

Synonyms: EGR-3, Early growth response protein 3, Egr-3
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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 [1].
  • Transfection studies in primary hippocampal neurons show that inducible early growth response factor 3 (Egr3) up-regulates GABRA4p activity as well as the levels of endogenous alpha4 subunits [2].
  • We now report that this complex contains a truncated isoform of Egr3 generated by use of an alternate translation start site at methionine 106 [3].
  • Full-length and truncated (missing residues 1 to 105) Egr3 isoforms differ in the ability to stimulate transcription directed by a tandem repeat of two EREs but not by a single ERE [3].
  • Gel shift assays demonstrated that Egr-1 and Egr-3 DNA binding activities follow the same pattern [4].

Biological context of Egr3

  • Here, we report the rat cDNA sequence of a zinc-finger transcription factor, Egr3/Pilot, and characterize its regulated mRNA expression in brain [5].
  • These findings indicate that Egr-1 and Egr-3 act in concert to mediate early and late phases, respectively, of the transcriptional response regulated by their cognate response element [4].
  • Previous studies examining the regulation of immediate early gene mRNAs by neuronal stimulation have revealed that two members of the Egr family of transcription factors, Egr-1 and Egr-3, display parallel response patterns [4].

Anatomical context of Egr3

  • Egr3 mRNA is rapidly and transiently induced in neurons of the hippocampus and cortex by electroconvulsive seizure. mRNA levels peak 2 hr after the seizure and remain elevated for as long as 8 hr [5].
  • Basal levels of Egr3 mRNA in the cortex appear to be driven by natural synaptic activity because monocular deprivation rapidly decreases Egr3 mRNA in the deafferented visual cortex [5].
  • Egr3 mRNA is also rapidly induced in granule cells of the dentate gyrus by synaptic NMDA receptor activation elicited by patterned stimulation of the perforant pathway and by drugs that alter dopamine neurotransmission in the striatum [5].
  • Blocking Egr3 and Junb function by dominant-negative constructs reduced neurite outgrowth under stimulating conditions, proving that activation of members of both the Egr and Jun families is necessary for maximal PC12 cell response to NGF and BMP4 [6].
  • Bands composed, at least in part, of Egr-2 and Egr-3 were present in different relative amounts in the cerebral cortex, striatum, hippocampus, thalamus, and midbrain [7].

Associations of Egr3 with chemical compounds

  • Chronic ethanol has region-selective effects on Egr-1 and Egr-3 DNA-binding activity and protein expression in the rat brain [8].
  • Egr-3 displayed an expression profile similar to that of Egr-1 in response to acute cocaine injection and was expressed slightly earlier upon repeated cocaine treatment [9].

Other interactions of Egr3

  • Aspects of the protein structure, sequence-specific DNA binding, transcriptional activity, and regulation of Egr3 are highly similar to another zinc-finger transcription factor, Egr1/zif268 [5].
  • In contrast, the expression of EGR-2, EGR-3, and EGR-4 messenger RNA was not increased in the amygdala, hippocampus or cortex following fear conditioning [10].


  1. 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]
  2. Egr3 stimulation of GABRA4 promoter activity as a mechanism for seizure-induced up-regulation of GABA(A) receptor alpha4 subunit expression. Roberts, D.S., Raol, Y.H., Bandyopadhyay, S., Lund, I.V., Budreck, E.C., Passini, M.A., Passini, M.J., Wolfe, J.H., Brooks-Kayal, A.R., Russek, S.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. Major Egr3 isoforms are generated via alternate translation start sites and differ in their abilities to activate transcription. O'Donovan, K.J., Baraban, J.M. Mol. Cell. Biol. (1999) [Pubmed]
  4. Sequential expression of Egr-1 and Egr-3 in hippocampal granule cells following electroconvulsive stimulation. O'Donovan, K.J., Wilkens, E.P., Baraban, J.M. J. Neurochem. (1998) [Pubmed]
  5. Egr3/Pilot, a zinc finger transcription factor, is rapidly regulated by activity in brain neurons and colocalizes with Egr1/zif268. Yamagata, K., Kaufmann, W.E., Lanahan, A., Papapavlou, M., Barnes, C.A., Andreasson, K.I., Worley, P.F. Learn. Mem. (1994) [Pubmed]
  6. BMP enhances transcriptional responses to NGF during PC12 cell differentiation. Lönn, P., Zaia, K., Israelsson, C., Althini, S., Usoskin, D., Kylberg, A., Ebendal, T. Neurochem. Res. (2005) [Pubmed]
  7. Differential expression of Egr-1-like DNA-binding activities in the naive rat brain and after excitatory stimulation. Beckmann, A.M., Davidson, M.S., Goodenough, S., Wilce, P.A. J. Neurochem. (1997) [Pubmed]
  8. Chronic ethanol has region-selective effects on Egr-1 and Egr-3 DNA-binding activity and protein expression in the rat brain. Depaz, I.M., Goodenough, S., Wilce, P.A. Neurochem. Int. (2000) [Pubmed]
  9. Differential rat brain expression of EGR proteins and of the transcriptional corepressor NAB in response to acute or chronic cocaine administration. Jouvert, P., Dietrich, J.B., Aunis, D., Zwiller, J. Neuromolecular Med. (2002) [Pubmed]
  10. Specific induction of early growth response gene 1 in the lateral nucleus of the amygdala following contextual fear conditioning in rats. Malkani, S., Rosen, J.B. Neuroscience (2000) [Pubmed]
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