Gene Symbol: Egr3
Description: early growth response 3
Alias: Pilot, early growth response protein 3, EGR-3
Species: mouse
Products:     Egr3

Top Publications

  1. 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
    ..Here, we report that deletion of both transcription factors Egr2 and Egr3 in lymphocytes resulted in a lethal autoimmune syndrome with excessive serum proinflammatory cytokines but also ..
  2. 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. ..
  3. 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
    ..Here we report the characterization of a new member of the Egr family referred to as EGR3 (human). This cDNA clone was isolated using low stringency hybridization with the zinc finger domain of Egr-1...
  4. 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
    ..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...
  5. 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
    ..By engaging Skint-1(+) cells, Vγ5(+)Vδ1(+) thymocytes induced an Egr3-mediated pathway, provoking differentiation and the potential to produce IFN-γ while suppressing the γδ TÂ..
  6. 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
    ..b>Egr3-/- mice also display abnormal responses to novelty, including heightened reactivity to novel environments and ..
  7. 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
    ..Overexpression of Egr2 and Egr3 was associated with an increase in the E3 ubiquitin ligase Cbl-b and inhibition of T cell activation...
  8. Patel T, Kramer I, Kucera J, Niederkofler V, Jessell T, Arber S, et al. Peripheral NT3 signaling is required for ETS protein expression and central patterning of proprioceptive sensory afferents. Neuron. 2003;38:403-16 pubmed
    ..Finally, addition of NT3 to DRG explant cultures resulted in induction of ER81 protein. Our data indicate that NT3 mediates the formation of proprioceptive afferent-motor neuron connections via regulation of ER81. ..
  9. 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
    ..Here, we show that Egr1 and Egr3 directly regulate the plasticity-associated activity-regulated cytoskeletal-related (Arc) gene, a synaptic activity-..

More Information


  1. Shneider N, Mentis G, Schustak J, O Donovan M. Functionally reduced sensorimotor connections form with normal specificity despite abnormal muscle spindle development: the role of spindle-derived neurotrophin 3. J Neurosci. 2009;29:4719-35 pubmed publisher
    ..These findings indicate that spindle-derived factors regulate the strength of the connections but not their initial formation or their specificity. ..
  2. Whitehead J, Keller Peck C, Kucera J, Tourtellotte W. Glial cell-line derived neurotrophic factor-dependent fusimotor neuron survival during development. Mech Dev. 2005;122:27-41 pubmed
  3. Swirnoff A, Milbrandt J. DNA-binding specificity of NGFI-A and related zinc finger transcription factors. Mol Cell Biol. 1995;15:2275-87 pubmed the prototypic member of a family of immediate-early gene-encoded transcription factors which includes NGFI-C, Egr3, and Krox20...
  4. Arber S, Ladle D, Lin J, Frank E, Jessell T. ETS gene Er81 controls the formation of functional connections between group Ia sensory afferents and motor neurons. Cell. 2000;101:485-98 pubmed
    ..ER81 therefore controls a late step in the establishment of functional sensory-motor circuitry in the developing spinal cord. ..
  5. 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
    ..To address whether spindles, in turn, regulate the function of Ia afferents, we examined Egr3-null mutant mice (Egr3-/-), in which muscle spindles degenerate progressively after birth...
  6. 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
    ..The zinc finger transcription factor, early growth response gene 3 (Egr3), is selectively expressed in sensory axon-contacted myotubes, and it is required for normal intrafusal muscle ..
  7. 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
    ..Here we show that Egr3, a transcriptional regulator closely related to Egr1, is essential for normal hippocampal long-term potentiation (..
  8. 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
    ..Here, we identify Egr3, a member of the early growth response (Egr) family of transcriptional regulators, as having an important role in ..
  9. 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
    The Egr family of zinc-finger transcription factors, consisting of Egr1, Egr2, Egr3, and Egr4, are involved in cellular growth and differentiation...
  10. Tourtellotte W, Milbrandt J. Sensory ataxia and muscle spindle agenesis in mice lacking the transcription factor Egr3. Nat Genet. 1998;20:87-91 pubmed
    ..The Egr family of zinc-finger transcription factors, whose members include Egr1 (NGFI-A), Egr2 (Krox-20), Egr3 and Egr4 (NGFI-C), are thought to regulate critical genetic programs involved in cellular growth and ..
  11. Lazarevic V, Zullo A, Schweitzer M, Staton T, Gallo E, Crabtree G, et al. The gene encoding early growth response 2, a target of the transcription factor NFAT, is required for the development and maturation of natural killer T cells. Nat Immunol. 2009;10:306-13 pubmed publisher
    ..NKT cells developed normally in the absence of Egr1 or Egr3, which suggests that Egr2 is a specific regulator of NKT cell differentiation...
  12. Quach D, Oliveira Fernandes M, Gruner K, Tourtellotte W. A sympathetic neuron autonomous role for Egr3-mediated gene regulation in dendrite morphogenesis and target tissue innervation. J Neurosci. 2013;33:4570-83 pubmed publisher
    b>Egr3 is a nerve growth factor (NGF)-induced transcriptional regulator that is essential for normal sympathetic nervous system development...
  13. 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
    ..Here we show that mice lacking the IEG transcription factor Egr3 (Egr3-/- mice) display increased aggression, and a decreased latency to attack, in response to the stressful social ..
  14. Xi H, Kersh G. Early growth response gene 3 regulates thymocyte proliferation during the transition from CD4-CD8- to CD4+CD8+. J Immunol. 2004;172:964-71 pubmed
    ..We have evaluated the role played by early growth response gene 3 (Egr3) in translating pre-TCR signals into differentiation and proliferation...
  15. Williams S, Jacobson C. ?-Dystroglycan is essential for the induction of Egr3, a transcription factor important in muscle spindle formation. Dev Neurobiol. 2010;70:498-507 pubmed publisher
    ..addressed potential roles for agrin (AGRN) and laminin (LN) in the expression of the transcription factor Egr3. Levels of Egr3 were monitored using immunoblot analysis and both basal lamina molecules proved effective in ..
  16. Shin H, Kwon S, Song H, Lim H. The transcription factor Egr3 is a putative component of the microtubule organizing center in mouse oocytes. PLoS ONE. 2014;9:e94708 pubmed publisher
    ..During an investigation of Egr factor localization in mouse ovaries, we noted that Egr3 exhibits a subcellular localization that overlaps with the meiotic spindle in oocytes...
  17. Chen X, Levedakou E, Millen K, Wollmann R, Soliven B, Popko B. Proprioceptive sensory neuropathy in mice with a mutation in the cytoplasmic Dynein heavy chain 1 gene. J Neurosci. 2007;27:14515-24 pubmed
    ..Together, we provide in vivo evidence that distinct mutations in cytoplasmic dynein can either result in a pure sensory neuropathy or in a sensory neuropathy with motor neuron involvement. ..
  18. Carter J, Tourtellotte W. Early growth response transcriptional regulators are dispensable for macrophage differentiation. J Immunol. 2007;178:3038-47 pubmed
    ..Egr1 and Egr3 expression was found to be induced in myeloid cells when they were differentiated into macrophages by treatment ..
  19. Enjin A, Leao K, Mikulovic S, Le Merre P, Tourtellotte W, Kullander K. Sensorimotor function is modulated by the serotonin receptor 1d, a novel marker for gamma motor neurons. Mol Cell Neurosci. 2012;49:322-32 pubmed publisher
  20. Cheng H, Hao S, Liu Y, Pang Y, Ma S, Dong F, et al. Leukemic marrow infiltration reveals a novel role for Egr3 as a potent inhibitor of normal hematopoietic stem cell proliferation. Blood. 2015;126:1302-13 pubmed publisher
    ..Gene expression profiling and further functional validation revealed that Egr3 was a strong limiting factor for the proliferative potential of HSCs...
  21. Grose R, Harris B, Cooper L, Topilko P, Martin P. Immediate early genes krox-24 and krox-20 are rapidly up-regulated after wounding in the embryonic and adult mouse. Dev Dyn. 2002;223:371-8 pubmed
    ..Despite the dramatic up-regulation of these genes in response to injury, our studies reveal that neither of them on their own is essential for repair. ..
  22. Ashrafi S, Lalancette Hébert M, Friese A, Sigrist M, Arber S, Shneider N, et al. Wnt7A identifies embryonic ?-motor neurons and reveals early postnatal dependence of ?-motor neurons on a muscle spindle-derived signal. J Neurosci. 2012;32:8725-31 pubmed publisher
    ..Furthermore, using Wnt7a expression as an early marker of ?-MN identity, we demonstrate a previously unknown dependence of ?-MNs on a muscle spindle-derived, GDNF-independent signal during the first postnatal week. ..
  23. Cheret C, Willem M, Fricker F, Wende H, Wulf Goldenberg A, Tahirovic S, et al. Bace1 and Neuregulin-1 cooperate to control formation and maintenance of muscle spindles. EMBO J. 2013;32:2015-28 pubmed publisher
    ..Our results assign to Bace1 a role in the control of coordinated movement through its regulation of muscle spindle physiology, and implicate IgNrg1-dependent processing as a molecular mechanism. ..
  24. 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. ..
  25. 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. ..
  26. Chandra R, Francis T, Konkalmatt P, Amgalan A, Gancarz A, Dietz D, et al. Opposing role for Egr3 in nucleus accumbens cell subtypes in cocaine action. J Neurosci. 2015;35:7927-37 pubmed publisher
    ..mechanisms occurring in MSN subtypes by cocaine, we examined the transcription factor early growth response 3 (Egr3)...
  27. Herdegen T, Leah J. Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Brain Res Rev. 1998;28:370-490 pubmed
    ..We also describe their expression and possible roles in glial cells. Finally, we discuss the relevance of their expression for nervous system functioning under normal and patho-physiological conditions. ..
  28. 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. ..
  29. Basaldella E, Takeoka A, Sigrist M, Arber S. Multisensory Signaling Shapes Vestibulo-Motor Circuit Specificity. Cell. 2015;163:301-12 pubmed publisher
    ..Thus, two sensory signaling systems interact to establish complementary synaptic input patterns to the final site of motor output processing. ..
  30. Maple A, Zhao X, Elizalde D, McBride A, Gallitano A. Htr2a Expression Responds Rapidly to Environmental Stimuli in an Egr3-Dependent Manner. ACS Chem Neurosci. 2015;6:1137-42 pubmed publisher
    ..This effect requires the immediate early gene early growth response 3 (Egr3), as sleep deprivation failed to induce Htr2a expression in Egr3-/- mice...
  31. Adikusuma F, Pederick D, McAninch D, Hughes J, Thomas P. Functional Equivalence of the SOX2 and SOX3 Transcription Factors in the Developing Mouse Brain and Testes. Genetics. 2017;206:1495-1503 pubmed publisher
    ..Together, these in vivo data provide strong evidence that SOX2 and SOX3 proteins are functionally equivalent. ..
  32. 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
    ..found that CD4(+)CD25(-)CD45RO(-)lymphocyte activation gene 3 (LAG3)(-) T cells express membrane-bound TGF-?1 in an EGR3-dependent manner...
  33. Carter J, Lefebvre J, Wiest D, Tourtellotte W. Redundant role for early growth response transcriptional regulators in thymocyte differentiation and survival. J Immunol. 2007;178:6796-805 pubmed
    ..Three Egr proteins, Egr1, Egr2, and Egr3, are induced during thymocyte differentiation in response to pre-TCR signaling, suggesting they may be critical for ..
  34. Herndon C, Ankenbruck N, Fromm L. The Erk MAP kinase pathway is activated at muscle spindles and is required for induction of the muscle spindle-specific gene Egr3 by neuregulin1. J Neurosci Res. 2014;92:174-84 pubmed publisher
    ..The transcription factor Egr3 is transcriptionally induced by NRG1, which in turn activates various target genes involved in forming intrafusal ..
  35. Yoo Y, Lee M. Hepatitis B virus X protein induces expression of Fas ligand gene through enhancing transcriptional activity of early growth response factor. J Biol Chem. 2004;279:36242-9 pubmed
    ..Taken together, our results show a novel mechanism by which HBx induces FasL gene expression that is mediated by enhancing transcriptional activity of Egr-2 and Egr-3. ..
  36. Oliveira Fernandes M, Tourtellotte W. Egr3-dependent muscle spindle stretch receptor intrafusal muscle fiber differentiation and fusimotor innervation homeostasis. J Neurosci. 2015;35:5566-78 pubmed publisher
    ..The transcriptional regulator Egr3 is induced in Ia-afferent contacted myotubes by Neuregulin1 (Nrg1)/ErbB receptor signaling and it has an essential ..
  37. Li L, ELDREDGE L, Quach D, Honasoge A, Gruner K, Tourtellotte W. Egr3 dependent sympathetic target tissue innervation in the absence of neuron death. PLoS ONE. 2011;6:e25696 pubmed publisher
    ..b>Egr3 is a transcription factor regulated by NGF signaling in sympathetic neurons that is essential for normal SNS ..
  38. Mayer S, Rössler O, Endo T, Charnay P, Thiel G. Epidermal-growth-factor-induced proliferation of astrocytes requires Egr transcription factors. J Cell Sci. 2009;122:3340-50 pubmed publisher
    ..Together, these data show that Egr transcription factors are essential for conversion of the mitogenic signal of EGF into a proliferative response. ..
  39. Maple A, Lackie R, Elizalde D, Grella S, Damphousse C, Xa C, et al. Attenuated Late-Phase Arc Transcription in the Dentate Gyrus of Mice Lacking Egr3. Neural Plast. 2017;2017:6063048 pubmed publisher
    ..Animals lacking Egr3 show less Arc expression following convulsive stimulation, but the effect of Egr3 ablation on ..
  40. Parkinson R, Collins S, Horton M, Powell J. Egr3 induces a Th17 response by promoting the development of ?? T cells. PLoS ONE. 2014;9:e87265 pubmed publisher
    The transcription factor Early Growth Response 3 (Egr3) has been shown to play an important role in negatively regulating T cell activation and promoting T cell anergy in Th1 cells...
  41. Takeoka A, Vollenweider I, Courtine G, Arber S. Muscle spindle feedback directs locomotor recovery and circuit reorganization after spinal cord injury. Cell. 2014;159:1626-39 pubmed publisher
    ..Our findings reveal an essential role for muscle spindle feedback in directing basic locomotor recovery and facilitating circuit reorganization after spinal cord injury. ..
  42. 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
    The immediate-early gene early growth response 3 (Egr3) is associated with schizophrenia and expressed at reduced levels in postmortem patients' brains...
  43. Lalancette Hébert M, Sharma A, Lyashchenko A, Shneider N. Gamma motor neurons survive and exacerbate alpha motor neuron degeneration in ALS. Proc Natl Acad Sci U S A. 2016;113:E8316-E8325 pubmed publisher
    ..This study establishes the resistance of γ-MNs as a general feature of ALS mouse models and demonstrates that synaptic excitation of MNs within a complex circuit is an important determinant of relative vulnerability in ALS. ..
  44. 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
    ..b>Egr3 knockout mice, lacking muscle spindles, but not Golgi tendon organs, displayed a less severe phenotype, suggesting ..
  45. Miao T, Symonds A, Singh R, Symonds J, Ogbe A, Omodho B, et al. Egr2 and 3 control adaptive immune responses by temporally uncoupling expansion from T cell differentiation. J Exp Med. 2017;214:1787-1808 pubmed publisher
    ..Thus, Egr2 and 3 are upstream regulators of effector CD4 and CD8 T cells that are essential for optimal responses with limited immunopathology. ..
  46. Morita K, Okamura T, Inoue M, Komai T, Teruya S, Iwasaki Y, et al. Egr2 and Egr3 in regulatory T cells cooperatively control systemic autoimmunity through Ltbp3-mediated TGF-β3 production. Proc Natl Acad Sci U S A. 2016;113:E8131-E8140 pubmed
    ..Here, we show that Egr2 and Egr3 expressed in T cells cooperatively prevent humoral immune responses by supporting TGF-β3 secretion...
  47. Gao X, Daugherty R, Tourtellotte W. Regulation of low affinity neurotrophin receptor (p75(NTR)) by early growth response (Egr) transcriptional regulators. Mol Cell Neurosci. 2007;36:501-14 pubmed
    ..Here, we identify the early growth response (Egr) transcriptional regulators, Egr1 and Egr3, as direct modulators of p75(NTR) gene expression...
  48. 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. ..
  49. Kurosaka M, Ogura Y, Funabashi T, Akema T. Early Growth Response 3 (Egr3) Contributes a Maintenance of C2C12 Myoblast Proliferation. J Cell Physiol. 2017;232:1114-1122 pubmed publisher
    ..However, its regulatory mechanisms remain unknown. Early growth response 3 (Egr3) is a zinc-finger transcription factor that regulates different cellular functions...
  50. Ogbe A, Miao T, Symonds A, Omodho B, Singh R, Bhullar P, et al. Early Growth Response Genes 2 and 3 Regulate the Expression of Bcl6 and Differentiation of T Follicular Helper Cells. J Biol Chem. 2015;290:20455-65 pubmed publisher
    ..We have now discovered that early growth response gene 2 (EGR2) and EGR3 directly regulate the expression of Bcl6 in Tfh cells, which is required for their function in regulation of GC ..
  51. Kearney S, Delgado C, Eshleman E, Hill K, O Connor B, Lenz L. Type I IFNs downregulate myeloid cell IFN-? receptor by inducing recruitment of an early growth response 3/NGFI-A binding protein 1 complex that silences ifngr1 transcription. J Immunol. 2013;191:3384-92 pubmed publisher
    ..Egr proteins and two Egr/NGFI-A binding (Nab) proteins were found to be expressed in bone macrophages, but only Egr3 and Nab1 were recruited to the ifngr1 promoter upon IFN-? stimulation...
  52. Shneider N, Brown M, Smith C, Pickel J, Alvarez F. Gamma motor neurons express distinct genetic markers at birth and require muscle spindle-derived GDNF for postnatal survival. Neural Dev. 2009;4:42 pubmed publisher
    ..This provides a mouse model with which to explore the specific role of gamma-fusimotor activity in motor behaviors. ..
  53. Knight R, Panopoulou G, Holland P, Shimeld S. An amphioxus Krox gene: insights into vertebrate hindbrain evolution. Dev Genes Evol. 2000;210:518-21 pubmed
  54. Fang F, Shangguan A, Kelly K, Wei J, Gruner K, Ye B, et al. Early growth response 3 (Egr-3) is induced by transforming growth factor-? and regulates fibrogenic responses. Am J Pathol. 2013;183:1197-1208 pubmed publisher