early growth response protein 3


Summary: An early growth response transcription factor that is essential for the development of MUSCLE SPINDLES.

Top Publications

  1. ELDREDGE L, Gao X, Quach D, Li L, Han X, Lomasney J, et al. Abnormal sympathetic nervous system development and physiological dysautonomia in Egr3-deficient mice. Development. 2008;135:2949-57 pubmed publisher
    ..Egr3-deficient mice have a phenotype that is remarkably similar to humans with sympathetic nervous system disease, raising the possibility that it may have a role in some forms of human dysautonomia, most of which have no known cause. ..
  2. Sela U, Dayan M, Hershkoviz R, Lider O, Mozes E. A peptide that ameliorates lupus up-regulates the diminished expression of early growth response factors 2 and 3. J Immunol. 2008;180:1584-91 pubmed
    ..Thus, hCDR1 down-regulates Akt phosphorylation, which leads to up-regulated expression of T cell Egr-2 and Egr-3, resulting in the inhibition of IFN-gamma secretion that is required for the maintenance of SLE. ..
  3. Collins S, Lutz M, Zarek P, Anders R, Kersh G, Powell J. Opposing regulation of T cell function by Egr-1/NAB2 and Egr-2/Egr-3. Eur J Immunol. 2008;38:528-36 pubmed publisher
    ..Overall, our data suggest that just as the Egr/NAB network of genes control cell fate in other systems, TCR-induced Egr-1, 2, 3 and NAB2 control the fate of antigen recognition in T cells. ..
  4. Yamada K, Gerber D, Iwayama Y, Ohnishi T, Ohba H, Toyota T, et al. Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia. Proc Natl Acad Sci U S A. 2007;104:2815-20 pubmed
    ..These findings support the previous genetic association of altered calcineurin signaling with schizophrenia pathogenesis and identify EGR3 as a compelling susceptibility gene. ..
  5. Li L, Yun S, Keblesh J, Trommer B, Xiong H, Radulovic J, et al. Egr3, a synaptic activity regulated transcription factor that is essential for learning and memory. Mol Cell Neurosci. 2007;35:76-88 pubmed
    ..Thus, Egr3 has an essential role in learning and memory processing that appears to be partly distinct from the role of Egr1. ..
  6. Swirnoff A, Milbrandt J. DNA-binding specificity of NGFI-A and related zinc finger transcription factors. Mol Cell Biol. 1995;15:2275-87 pubmed
    ..Furthermore, we show that this affinity difference is a property not of the zinc fingers themselves but rather of the protein context of the DNA-binding domain. ..
  7. Liu D, Evans I, Britton G, Zachary I. The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis. Oncogene. 2008;27:2989-98 pubmed
  8. Gallitano Mendel A, Izumi Y, Tokuda K, Zorumski C, Howell M, Muglia L, et al. The immediate early gene early growth response gene 3 mediates adaptation to stress and novelty. Neuroscience. 2007;148:633-43 pubmed
    ..These findings are the first demonstration of the requirement for an IEG-TF in mediating the response to stress and novelty, and in the establishment of LTD. ..
  9. Suzuki T, Inoue A, Miki Y, Moriya T, Akahira J, Ishida T, et al. Early growth responsive gene 3 in human breast carcinoma: a regulator of estrogen-meditated invasion and a potent prognostic factor. Endocr Relat Cancer. 2007;14:279-92 pubmed
    ..These results suggest that EGR3 plays an important role in estrogen-meditated invasion and is an independent prognostic factor in breast carcinoma. ..

More Information


  1. Gallitano Mendel A, Wozniak D, Pehek E, Milbrandt J. Mice lacking the immediate early gene Egr3 respond to the anti-aggressive effects of clozapine yet are relatively resistant to its sedating effects. Neuropsychopharmacology. 2008;33:1266-75 pubmed
    ..This suggests the possibility that Egr3-/- mice may provide insight into the neurobiological abnormalities underlying schizophrenia. ..
  2. Roberts D, Hu Y, Lund I, Brooks Kayal A, Russek S. Brain-derived neurotrophic factor (BDNF)-induced synthesis of early growth response factor 3 (Egr3) controls the levels of type A GABA receptor alpha 4 subunits in hippocampal neurons. J Biol Chem. 2006;281:29431-5 pubmed
  3. Xi H, Schwartz R, Engel I, Murre C, Kersh G. Interplay between RORgammat, Egr3, and E proteins controls proliferation in response to pre-TCR signals. Immunity. 2006;24:813-26 pubmed
    ..After Egr3 subsided, the expression and function of RORgammat increased. Thus, transient induction of Egr3 delays the effects of RORgammat and enables pre-TCR signaling to induce both proliferation and gene rearrangement. ..
  4. Safford M, Collins S, Lutz M, Allen A, Huang C, Kowalski J, et al. Egr-2 and Egr-3 are negative regulators of T cell activation. Nat Immunol. 2005;6:472-80 pubmed
    ..These data support the idea that Egr-2 and Egr-3 are involved in promoting a T cell receptor-induced negative regulatory genetic program. ..
  5. Droin N, Pinkoski M, Dejardin E, Green D. Egr family members regulate nonlymphoid expression of Fas ligand, TRAIL, and tumor necrosis factor during immune responses. Mol Cell Biol. 2003;23:7638-47 pubmed
    ..These results support a role for Egr family members in nonlymphoid expression of FasL, TRAIL, and TNF. ..
  6. Hippenmeyer S, Shneider N, Birchmeier C, Burden S, Jessell T, Arber S. A role for neuregulin1 signaling in muscle spindle differentiation. Neuron. 2002;36:1035-49 pubmed
  7. Tourtellotte W, Keller Peck C, Milbrandt J, Kucera J. The transcription factor Egr3 modulates sensory axon-myotube interactions during muscle spindle morphogenesis. Dev Biol. 2001;232:388-99 pubmed
    ..We conclude that Egr3 has an essential role in regulating genes required for the transformation of undifferentiated myotubes into intrafusal fibers, and hence for the phenotypic differentiation of spindles. ..
  8. Tourtellotte W, Milbrandt J. Sensory ataxia and muscle spindle agenesis in mice lacking the transcription factor Egr3. Nat Genet. 1998;20:87-91 pubmed
    ..These results indicate that type I myotubes are dependent upon Egr3-mediated transcription for proper spindle development. ..
  9. Roberts D, Raol Y, Bandyopadhyay S, Lund I, Budreck E, Passini M, et al. Egr3 stimulation of GABRA4 promoter activity as a mechanism for seizure-induced up-regulation of GABA(A) receptor alpha4 subunit expression. Proc Natl Acad Sci U S A. 2005;102:11894-9 pubmed
  10. Kim S, Song J, Joo E, Lee K, Ahn Y, Kim Y. EGR3 as a potential susceptibility gene for schizophrenia in Korea. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:1355-60 pubmed publisher
    ..Taken together, EGR3 could be suggested as a compelling susceptibility gene in schizophrenia. ..
  11. Kyogoku C, Yanagi M, Nishimura K, Sugiyama D, Morinobu A, Fukutake M, et al. Association of calcineurin A gamma subunit (PPP3CC) and early growth response 3 (EGR3) gene polymorphisms with susceptibility to schizophrenia in a Japanese population. Psychiatry Res. 2011;185:16-9 pubmed publisher
    ..12, p=0.01). ..
  12. Suehiro J, Hamakubo T, Kodama T, Aird W, Minami T. Vascular endothelial growth factor activation of endothelial cells is mediated by early growth response-3. Blood. 2010;115:2520-32 pubmed publisher
    ..Together, these findings suggest that Egr-3 is a critical determinant of VEGF signaling in activated endothelial cells. Thus, Egr-3 represents a potential therapeutic target in VEGF-mediated vasculopathic diseases. ..
  13. Li L, Carter J, Gao X, Whitehead J, Tourtellotte W. The neuroplasticity-associated arc gene is a direct transcriptional target of early growth response (Egr) transcription factors. Mol Cell Biol. 2005;25:10286-300 pubmed
    ..Thus, Egr1 and Egr3 can indirectly modulate synaptic plasticity by directly regulating Arc and the plasticity mechanisms it mediates in recently activated synapses. ..
  14. Albert Y, Whitehead J, Eldredge L, Carter J, Gao X, Tourtellotte W. Transcriptional regulation of myotube fate specification and intrafusal muscle fiber morphogenesis. J Cell Biol. 2005;169:257-68 pubmed
    ..Hence, Egr3 is a target gene that is regulated by sensory innervation and that mediates gene expression involved in myotube fate specification and intrafusal muscle fiber morphogenesis. ..
  15. Jacobson C, Duggan D, Fischbach G. Neuregulin induces the expression of transcription factors and myosin heavy chains typical of muscle spindles in cultured human muscle. Proc Natl Acad Sci U S A. 2004;101:12218-23 pubmed
    ..Taken together, these results indicate that not only can NRG induce the expression of a transcription factor key to spindle fiber development (Egr3), but that a portion of this developmental process can be replicated in vitro. ..
  16. Chen H, Tourtellotte W, Frank E. Muscle spindle-derived neurotrophin 3 regulates synaptic connectivity between muscle sensory and motor neurons. J Neurosci. 2002;22:3512-9 pubmed
    ..Intramuscular injections of NT3 to Egr3-/- mice during the postnatal period restored sensory-motor connections. Thus, NT3 derived from muscle spindles regulates the synaptic connectivity between muscle sensory and motor neurons. ..
  17. Wieland G, Nehmann N, Müller D, Eibel H, Siebenlist U, Sühnel J, et al. Early growth response proteins EGR-4 and EGR-3 interact with immune inflammatory mediators NF-kappaB p50 and p65. J Cell Sci. 2005;118:3203-12 pubmed
    ..In summary, in T cells, the two zinc-finger proteins EGR-4 and EGR-3 interact with the specific nuclear mediator NF-kappaB and control transcription of genes encoding inflammatory cytokines. ..
  18. Carleton M, Haks M, Smeele S, Jones A, Belkowski S, Berger M, et al. Early growth response transcription factors are required for development of CD4(-)CD8(-) thymocytes to the CD4(+)CD8(+) stage. J Immunol. 2002;168:1649-58 pubmed
    ..Taken together, these data demonstrate that the Egr proteins play an essential role in executing the differentiation program initiated by pre-TCR signaling. ..
  19. Sumitomo S, Fujio K, Okamura T, Morita K, Ishigaki K, Suzukawa K, et al. Transcription factor early growth response 3 is associated with the TGF-?1 expression and the regulatory activity of CD4-positive T cells in vivo. J Immunol. 2013;191:2351-9 pubmed publisher
    ..Our results suggest that Egr-3 is a transcription factor associated with TGF-?1 expression and in vivo regulatory activity in both mice and humans. ..
  20. Zhang R, Lu S, Meng L, Min Z, Tian J, Valenzuela R, et al. Genetic evidence for the association between the early growth response 3 (EGR3) gene and schizophrenia. PLoS ONE. 2012;7:e30237 pubmed publisher
  21. Mataga N, Fujishima S, Condie B, Hensch T. Experience-dependent plasticity of mouse visual cortex in the absence of the neuronal activity-dependent marker egr1/zif268. J Neurosci. 2001;21:9724-32 pubmed
    ..Our findings underscore a mechanistic distinction between sensory plasticity and long-lasting forms of synaptic potentiation in the hippocampus, for which egr1/zif268 was recently found to be essential. ..
  22. Turchinovich G, Hayday A. Skint-1 identifies a common molecular mechanism for the development of interferon-γ-secreting versus interleukin-17-secreting γδ T cells. Immunity. 2011;35:59-68 pubmed publisher
  23. Liu D, Jia H, Holmes D, Stannard A, Zachary I. Vascular endothelial growth factor-regulated gene expression in endothelial cells: KDR-mediated induction of Egr3 and the related nuclear receptors Nur77, Nurr1, and Nor1. Arterioscler Thromb Vasc Biol. 2003;23:2002-7 pubmed
    ..VEGF induces expression of NR4A nuclear receptors and Egr3 via KDR and KDR-mediated signaling mechanisms. The genes identified here are novel candidates as key early mediators of VEGF-induced endothelial functions. ..
  24. Dagai L, Peri Naor R, Birk R. Docosahexaenoic acid significantly stimulates immediate early response genes and neurite outgrowth. Neurochem Res. 2009;34:867-75 pubmed publisher
    ..5 and 1 h post-supplementation (respectively). In conclusion, we show that DHA significantly stimulates immediate-early neurogenesis events, as is evident by both morphological and molecular markers. ..
  25. Blecher R, Krief S, Galili T, Biton I, Stern T, Assaraf E, et al. The Proprioceptive System Masterminds Spinal Alignment: Insight into the Mechanism of Scoliosis. Dev Cell. 2017;42:388-399.e3 pubmed publisher
    ..These findings uncover a central role for the proprioceptive system in maintaining spinal alignment. ..
  26. Weigelt K, Carvalho L, Drexhage R, Wijkhuijs A, de Wit H, van Beveren N, et al. TREM-1 and DAP12 expression in monocytes of patients with severe psychiatric disorders. EGR3, ATF3 and PU.1 as important transcription factors. Brain Behav Immun. 2011;25:1162-9 pubmed publisher
    ..Our observations support the concept that monocytes are in a pro-inflammatory state in severe psychiatric conditions and suggest differences in monocyte inflammatory set points between SCZ, BD and MDD. ..
  27. Wang Z, Li L, Frank E. The role of muscle spindles in the development of the monosynaptic stretch reflex. J Neurophysiol. 2012;108:83-90 pubmed publisher
  28. To S, Knower K, Clyne C. NF?B and MAPK signalling pathways mediate TNF?-induced Early Growth Response gene transcription leading to aromatase expression. Biochem Biophys Res Commun. 2013;433:96-101 pubmed publisher
    ..4. ..
  29. Singh R, Miao T, Symonds A, Omodho B, Li S, Wang P. Egr2 and 3 Inhibit T-bet-Mediated IFN-? Production in T Cells. J Immunol. 2017;198:4394-4402 pubmed publisher
    ..Thus, Egr2 and 3 are antagonists of T-bet function in effector T cells and are important for the control of inflammatory responses of T cells. ..
  30. Yasunaga J, Taniguchi Y, Nosaka K, Yoshida M, Satou Y, Sakai T, et al. Identification of aberrantly methylated genes in association with adult T-cell leukemia. Cancer Res. 2004;64:6002-9 pubmed
  31. Mittelstadt P, Ashwell J. Role of Egr-2 in up-regulation of Fas ligand in normal T cells and aberrant double-negative lpr and gld T cells. J Biol Chem. 1999;274:3222-7 pubmed
    ..Thus, Egr-2, in addition to Egr-3, regulates FasL expression in activated normal T cells, and Egr-2 is likely to play a direct role in aberrant fasL up-regulation in lpr/lpr and gld/gld CD4(-)CD8(-) T cells. ..
  32. Rengarajan J, Mittelstadt P, Mages H, Gerth A, Kroczek R, Ashwell J, et al. Sequential involvement of NFAT and Egr transcription factors in FasL regulation. Immunity. 2000;12:293-300 pubmed
    ..Further, Egr3 expression is enriched in Th1 cells, suggesting a molecular basis for the known preferential expression of FasL in the Th1 versus Th2 subset. ..
  33. Jiang Y, Yamamoto M, Tanaka F, Ishigaki S, Katsuno M, Adachi H, et al. Gene expressions specifically detected in motor neurons (dynactin 1, early growth response 3, acetyl-CoA transporter, death receptor 5, and cyclin C) differentially correlate to pathologic markers in sporadic amyotrophic lateral sclerosis. J Neuropathol Exp Neurol. 2007;66:617-27 pubmed
    ..The sequence of motor neuron-specific gene expression changes in sporadic ALS can be beneficial information in developing appropriate therapeutic strategies for neurodegeneration. ..
  34. Kress E, Hedges J, Jutila M. Distinct gene expression in human Vdelta1 and Vdelta2 gammadelta T cells following non-TCR agonist stimulation. Mol Immunol. 2006;43:2002-11 pubmed
    ..The patterns of differentially expressed genes are consistent with unique functional roles for these cells in vivo. ..
  35. Castellanos M, López Giral S, López Cabrera M, de Landázuri M. Multiple cis-acting elements regulate the expression of the early T cell activation antigen CD69. Eur J Immunol. 2002;32:3108-17 pubmed
    ..These results indicate that the inducible expression of CD69 gene by mitogenic signals is regulated by multiple cis-acting elements and by the interplay of transcription factors of the AP-1, EGR and ATF/CREB families. ..
  36. Morris M, Viswanathan N, Kuhlman S, Davis F, Weitz C. A screen for genes induced in the suprachiasmatic nucleus by light. Science. 1998;279:1544-7 pubmed
    ..In contrast to known examples, egr-3 induction by light is restricted to the ventral SCN, a structure implicated in entrainment. ..
  37. Cron R, Bandyopadhyay R, Genin A, Brunner M, Kersh G, Yin J, et al. Early growth response-1 is required for CD154 transcription. J Immunol. 2006;176:811-8 pubmed
    ..This has implications for selective targeting of Egr family members to control abnormal expression of CD154 in autoimmune diseases such as systemic lupus erythematosus. ..
  38. Li S, Miao T, Sebastian M, Bhullar P, Ghaffari E, Liu M, et al. The transcription factors Egr2 and Egr3 are essential for the control of inflammation and antigen-induced proliferation of B and T cells. Immunity. 2012;37:685-96 pubmed publisher
    ..Thus, Egr2 and Egr3 regulate B and T cell function in adaptive immune responses and homeostasis by promoting antigen receptor signaling and controlling inflammation. ..
  39. Hinze A, Mayer P, Harst A, von Kugelgen I. Adenosine A(3) receptor-induced proliferation of primary human coronary smooth muscle cells involving the induction of early growth response genes. J Mol Cell Cardiol. 2012;53:639-45 pubmed publisher
    ..The results facilitate the understanding of the role of adenosine A(3) receptors in the cardiovascular system. ..
  40. Raible D, Frey L, Cruz Del Angel Y, Russek S, Brooks Kayal A. GABA(A) receptor regulation after experimental traumatic brain injury. J Neurotrauma. 2012;29:2548-54 pubmed publisher
    ..These findings suggest that the activation of the JaK/STAT and Egr3 pathways after TBI may regulate injury-related changes in GABA(A)R subunit expression. ..
  41. Chen W, Liu W, Zhao Y, Zhou L, Zhang T, Chen G, et al. Induction, modulation and potential targets of miR-210 in pancreatic cancer cells. Hepatobiliary Pancreat Dis Int. 2012;11:319-24 pubmed
    ..Also, E2F3, EFNA3, GIT2, MNT, ZNF462 and EGR3 may be potential miR-210 targets in PC. ..
  42. Okumura A, Kato T, Hayakawa F, Kidokoro H, Kuno K, Watanabe K. A pilot study on umbilical venous level of natriuretic peptides in preterm infants and their relation to periventricular leukomalacia and antenatal complications. Brain Dev. 2002;24:30-2 pubmed
    ..Umbilical venous levels of natriuretic peptides were not useful to predict neurological outcome in preterm infants. ..
  43. Li J, Tu Y, Tong L, Zhang W, Zheng J, Wei Q. Immunosuppressive activity on the murine immune responses of glycyrol from Glycyrrhiza uralensis via inhibition of calcineurin activity. Pharm Biol. 2010;48:1177-84 pubmed publisher
    ..Calcineurin (CN), a unique protein phosphatase, plays an important role in immune regulation. Our laboratory has established an effective molecular drug-screening model based on CN activity...
  44. Mages H, Baag R, Steiner B, Kroczek R. Utilization of an NF-ATp binding promoter element for EGR3 expression in T cells but not fibroblasts provides a molecular model for the lymphoid cell-specific effect of cyclosporin A. Mol Cell Biol. 1998;18:7157-65 pubmed
    ..The differential usage of an NF-AT binding site explains the selective effect of CsA on EGR3 gene expression in T cells versus fibroblasts and may represent one of the basic mechanisms underlying the tissue specificity of CsA. ..
  45. Deguchi T, Fujimori K, Kawasaki T, Xianghai L, Yuba S. Expression patterns of the Egr1 and Egr3 genes during medaka embryonic development. Gene Expr Patterns. 2009;9:209-14 pubmed publisher
    ..By sectioning the whole-mount specimens, expression of both the egr1 and egr3 mRNAs were observed in the telencephalon, hypothalamus, and optic tectum. However, the positions at which the genes were expressed were different. ..
  46. Xu M, Sharma A, Wiest D, Sen J. Pre-TCR-induced beta-catenin facilitates traversal through beta-selection. J Immunol. 2009;182:751-8 pubmed
    ..Thus, we demonstrate that pre-TCR induced beta-catenin sustains expression of Egr genes that facilitate traversal through the beta-selection checkpoint. ..
  47. Johansson A, Helou K, Levan G. Cytogenetic localization of cancer-related genes in the rat and comparative mapping studies in human and mouse. Cytogenet Cell Genet. 1998;81:217-21 pubmed
    ..The remaining gene (Map1a) is involved in microtubule assembly. ..
  48. Patwardhan S, Gashler A, Siegel M, Chang L, Joseph L, Shows T, et al. EGR3, a novel member of the Egr family of genes encoding immediate-early transcription factors. Oncogene. 1991;6:917-28 pubmed
    ..The EGR3 gene has a single intron and maps to chromosome 8 at bands p21-23. ..
  49. Honkaniemi J, Zhang J, Longo F, Sharp F. Stress induces zinc finger immediate early genes in the rat adrenal gland. Brain Res. 2000;877:203-8 pubmed
  50. Williams A, Ingram W, LeVine S, Resnik J, Kamel C, Lish J, et al. Reduced levels of serotonin 2A receptors underlie resistance of Egr3-deficient mice to locomotor suppression by clozapine. Neuropsychopharmacology. 2012;37:2285-98 pubmed publisher
  51. Diao H, Li X, Hu S, Liu Y. Gene expression profiling combined with bioinformatics analysis identify biomarkers for Parkinson disease. PLoS ONE. 2012;7:e52319 pubmed publisher
    ..However, they regulated differentially expressed genes. In conclusion, we suggest that HLF, E2F1 and STAT4 may be used as molecular biomarkers for PD; however, more work is needed to validate our result. ..
  52. Herndon C, Ankenbruck N, Lester B, Bailey J, Fromm L. Neuregulin1 signaling targets SRF and CREB and activates the muscle spindle-specific gene Egr3 through a composite SRF-CREB-binding site. Exp Cell Res. 2013;319:718-30 pubmed publisher
    ..These results suggest that NRG1 induces expression of the muscle spindle-specific gene Egr3 by stimulating the transcriptional activity of CREB and SRF. ..
  53. Yang Y, Dong B, Mittelstadt P, Xiao H, Ashwell J. HIV Tat binds Egr proteins and enhances Egr-dependent transactivation of the Fas ligand promoter. J Biol Chem. 2002;277:19482-7 pubmed