immediate early genes


Summary: Genes that show rapid and transient expression in the absence of de novo protein synthesis. The term was originally used exclusively for viral genes where immediate-early referred to transcription immediately following virus integration into the host cell. It is also used to describe cellular genes which are expressed immediately after resting cells are stimulated by extracellular signals such as growth factors and neurotransmitters.

Top Publications

  1. Miyashita T, Kubik S, Lewandowski G, Guzowski J. Networks of neurons, networks of genes: an integrated view of memory consolidation. Neurobiol Learn Mem. 2008;89:269-84 pubmed
    ..Such an updating process may well recruit and use many of the plasticity mechanisms necessary for the initial encoding of memory. ..
  2. Kubik S, Miyashita T, Guzowski J. Using immediate-early genes to map hippocampal subregional functions. Learn Mem. 2007;14:758-70 pubmed
    ..In closing, we provide a framework for how cutting-edge IEG imaging and intervention techniques will likely contribute to better understanding of the specific functions of CA3 and other hippocampal subregions. ..
  3. Tullai J, Chen J, Schaffer M, Kamenetsky E, Kasif S, Cooper G. Glycogen synthase kinase-3 represses cyclic AMP response element-binding protein (CREB)-targeted immediate early genes in quiescent cells. J Biol Chem. 2007;282:9482-91 pubmed
    ..These results indicate that GSK-3 actively represses gene expression in quiescent cells, with inhibition of CREB playing a key role in this transcriptional response. ..
  4. Shires K, Aggleton J. Mapping immediate-early gene activity in the rat after place learning in a water-maze: the importance of matched control conditions. Eur J Neurosci. 2008;28:982-96 pubmed publisher
    ..Rather, the activity in combinations of regions, including prefrontal cortex, provides a stronger correlate of water-maze learning. ..
  5. Miyachi S, Hasegawa Y, Gerfen C. Coincident stimulation of convergent cortical inputs enhances immediate early gene induction in the striatum. Neuroscience. 2005;134:1013-22 pubmed
    The effect of coincident stimulation of convergent corticostriatal inputs was analyzed by the induction of immediate early genes in striatal neurons...
  6. Agbemafle B, Oesterreicher T, Shaw C, Henning S. Immediate early genes of glucocorticoid action on the developing intestine. Am J Physiol Gastrointest Liver Physiol. 2005;288:G897-906 pubmed
  7. Centini C, Pompeiano O. Sleep research in space: expression of immediate early genes in forebrain structures of rats during the nasa neurolab mission (STS-90). Arch Ital Biol. 2007;145:117-50 pubmed
  8. Qiao X, Lu J, Hofmann S. Gene expression profiling in a mouse model of infantile neuronal ceroid lipofuscinosis reveals upregulation of immediate early genes and mediators of the inflammatory response. BMC Neurosci. 2007;8:95 pubmed
    ..b>Immediate early genes (Arc, Cyr61, c-fos, jun-b, btg2, NR4A1) were among the first genes upregulated during the presymptomatic ..
  9. Fujita T, Ryser S, Piuz I, Schlegel W. Up-regulation of P-TEFb by the MEK1-extracellular signal-regulated kinase signaling pathway contributes to stimulated transcription elongation of immediate early genes in neuroendocrine cells. Mol Cell Biol. 2008;28:1630-43 pubmed function as a crucial C-terminal-domain (CTD) kinase for RNA polymerase II (Pol II) transcribing immediate early genes (IEGs) in neuroendocrine GH4C1 cells...

More Information


  1. Kiya T, Kunieda T, Kubo T. Inducible- and constitutive-type transcript variants of kakusei , a novel non-coding immediate early gene, in the honeybee brain. Insect Mol Biol. 2008;17:531-6 pubmed publisher
  2. Ren X, Uhler M. Microarray transfection analysis of conserved genomic sequences from three immediate early genes. Genomics. 2009;93:159-68 pubmed publisher
    ..cotransfection was used to functionally characterize conserved non-coding sequences (CNSs) of three immediate early genes: c-fos, JunB and EGR-1...
  3. Liu W, Chang Y, Wang C, Kou G, Lo C. Microarray and RT-PCR screening for white spot syndrome virus immediate-early genes in cycloheximide-treated shrimp. Virology. 2005;334:327-41 pubmed
  4. Lee S, Vasishtha M, Prywes R. Activation and repression of cellular immediate early genes by serum response factor cofactors. J Biol Chem. 2010;285:22036-49 pubmed publisher
    The induction of expression of many cellular immediate early genes (IEG) involves the transcription factor serum response factor (SRF)...
  5. Narayanan A, Nogueira M, Ruyechan W, Kristie T. Combinatorial transcription of herpes simplex virus and varicella zoster virus immediate early genes is strictly determined by the cellular coactivator HCF-1. J Biol Chem. 2005;280:1369-75 pubmed
    ..The requirements for this protein supports the model whereby the regulated transport of HCF-1 from the cytoplasm to the nucleus in sensory neurons may control IE gene expression and reactivation of these viruses from the latent state. ..
  6. Ferguson S, Robinson T. Amphetamine-evoked gene expression in striatopallidal neurons: regulation by corticostriatal afferents and the ERK/MAPK signaling cascade. J Neurochem. 2004;91:337-48 pubmed
    The environmental context in which psychostimulant drugs are experienced influences their ability to induce immediate early genes (IEGs) in the striatum...
  7. Ramanan N, Shen Y, Sarsfield S, Lemberger T, Schutz G, Linden D, et al. SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability. Nat Neurosci. 2005;8:759-67 pubmed
    ..These findings indicate that the transcriptional events underlying neuronal survival and plasticity are dissociable and that SRF plays a prominent role in use-dependent modification of synaptic strength in the adult brain. ..
  8. Gobeil F, Zhu T, Brault S, Geha A, Vazquez Tello A, Fortier A, et al. Nitric oxide signaling via nuclearized endothelial nitric-oxide synthase modulates expression of the immediate early genes iNOS and mPGES-1. J Biol Chem. 2006;281:16058-67 pubmed
    ..acid (LPA) resulted in LPA1 receptor-mediated and nitricoxide-dependent up-regulation of the immediate early genes iNOS (inducible nitric-oxide synthase (NOS)) and mPGES-1 (microsomal prostaglandin E synthase-1)...
  9. Guzowski J, Miyashita T, Chawla M, Sanderson J, Maes L, Houston F, et al. Recent behavioral history modifies coupling between cell activity and Arc gene transcription in hippocampal CA1 neurons. Proc Natl Acad Sci U S A. 2006;103:1077-82 pubmed
    ..This state-dependence of neuronal transcriptional coupling provides a mechanism of metaplasticity and may regulate capacity for synaptic modification in neural networks. ..
  10. Kinser S, Jia Q, Li M, Laughter A, Cornwell P, Corton J, et al. Gene expression profiling in spleens of deoxynivalenol-exposed mice: immediate early genes as primary targets. J Toxicol Environ Health A. 2004;67:1423-41 pubmed
    ..Taken together, data suggest that DON upregulated the expression of multiple immediate early genes, many of which are likely to contribute to the complex immunological effects reported for this and other ..
  11. Fujita T, Piuz I, Schlegel W. Negative elongation factor NELF controls transcription of immediate early genes in a stimulus-specific manner. Exp Cell Res. 2009;315:274-84 pubmed publisher
    The transcription rate of immediate early genes (IEGs) is controlled directly by transcription elongation factors at the transcription elongation step...
  12. Soule J, Penke Z, Kanhema T, Alme M, Laroche S, Bramham C. Object-place recognition learning triggers rapid induction of plasticity-related immediate early genes and synaptic proteins in the rat dentate gyrus. Neural Plast. 2008;2008:269097 pubmed publisher
    ..Here, we examined expression of the plasticity-associated immediate early genes (Arc, Zif268, and Narp) in the dentate gyrus following long-term object-place recognition learning in rats...
  13. Imam S, Duhart H, Skinner J, Ali S. Cocaine induces a differential dose-dependent alteration in the expression profile of immediate early genes, transcription factors, and caspases in PC12 cells: a possible mechanism of neurotoxic damage in cocaine addiction. Ann N Y Acad Sci. 2005;1053:482-90 pubmed
    ..In the present study, we evaluated the effect of increasing doses of cocaine on the expression of immediate early genes (IEGs), c-fos and c-jun, and closely related transcription factors, SP-1 and NF-kbeta, at 24 h after the ..
  14. Derfuss T, Segerer S, Herberger S, Sinicina I, Hüfner K, Ebelt K, et al. Presence of HSV-1 immediate early genes and clonally expanded T-cells with a memory effector phenotype in human trigeminal ganglia. Brain Pathol. 2007;17:389-98 pubmed
    ..Thus, HSV-1 IE genes are expressed in human TG and the infiltrating T-cells bear several characteristics that suggest viral antigenic stimulation. ..
  15. Richebe P, Rathmell J, Brennan T. Immediate early genes after pulsed radiofrequency treatment: neurobiology in need of clinical trials. Anesthesiology. 2005;102:1-3 pubmed
  16. Dickey C, De Mesquita D, Morgan D, Pennypacker K. Induction of memory-associated immediate early genes by nerve growth factor in rat primary cortical neurons and differentiated mouse Neuro2A cells. Neurosci Lett. 2004;366:10-4 pubmed
    Activation of several immediate early genes (IEGs) is crucial for long-term memory formation in vivo. In vitro methods of inducing these genes have not been investigated extensively...
  17. Cho Y, Gong T, Kanicki A, Altschuler R, Lomax M. Noise overstimulation induces immediate early genes in the rat cochlea. Brain Res Mol Brain Res. 2004;130:134-48 pubmed
    ..The intense PTS noise induced several immediate early genes encoding both transcription factors (c-FOS, EGR1, NUR77/TR3) and cytokines (PC3/BTG2, LIF and IP10)...
  18. Schmahl J, Raymond C, Soriano P. PDGF signaling specificity is mediated through multiple immediate early genes. Nat Genet. 2007;39:52-60 pubmed
    Growth factor signaling leads to the induction or repression of immediate early genes, but how these genes act collectively as effectors of downstream processes remains unresolved...
  19. Petrovich G, Holland P, Gallagher M. Amygdalar and prefrontal pathways to the lateral hypothalamus are activated by a learned cue that stimulates eating. J Neurosci. 2005;25:8295-302 pubmed
    ..Our results indicate that a cue that has acquired the ability to promote eating in sated rats (CS+) strongly activates a functional network formed by direct pathways from the BL/BM and orbitomedial prefrontal cortex to the LHA. ..
  20. Chen Y, Yao B, Zhu Z, Yi Y, Lin X, Zhang Z, et al. A constitutive super-enhancer: homologous region 3 of Bombyx mori nucleopolyhedrovirus. Biochem Biophys Res Commun. 2004;318:1039-44 pubmed
    ..The utilizing of this promoter-enhancer combination in the baculovirus expression vector system (BEVS) was also carried out to further confirm the function of hr3 enhancer. ..
  21. Sigworth L, Liao L, Chandler T, Geusz M. Luciferase expression controlled by a viral gene promoter in a mammalian circadian pacemaker. Neuroreport. 2003;14:443-7 pubmed
    ..Single-cell bioluminescence imaging revealed that the circadian pacemaker can regulate exogenous viral genes and could play a role in viral diseases. ..
  22. Bozon B, Davis S, Laroche S. A requirement for the immediate early gene zif268 in reconsolidation of recognition memory after retrieval. Neuron. 2003;40:695-701 pubmed
    ..These findings indicate that IEG-mediated transcriptional regulation in neurons is one common molecular mechanism for the storage of newly formed and reactivated recognition memories. ..
  23. Bozon B, Davis S, Laroche S. Regulated transcription of the immediate-early gene Zif268: mechanisms and gene dosage-dependent function in synaptic plasticity and memory formation. Hippocampus. 2002;12:570-7 pubmed
    ..We show that spatial learning is particularly sensitive to reduced levels of Zif268, as one-half of the complement of Zif268 in heterozygous mice is insufficient to maintain spatial long-term memories. ..
  24. de Bartolomeis A, Iasevoli F. The Homer family and the signal transduction system at glutamatergic postsynaptic density: potential role in behavior and pharmacotherapy. Psychopharmacol Bull. 2003;37:51-83 pubmed
    ..Homer-regulated PSD remodeling may represent a mechanism of synaptic plasticity and a putative target for both pharmacotherapy and pharmacogenomics of behavioral disorders. ..
  25. Jessberger S, Kempermann G. Adult-born hippocampal neurons mature into activity-dependent responsiveness. Eur J Neurosci. 2003;18:2707-12 pubmed
    ..Thus, new neurons appear quantitatively integrated into hippocampal circuits, suggestive of a relevant contribution to hippocampal function. ..
  26. Taguchi T, Shima Y, Nakao M, Fujii Y, Tajiri T, Ogita K, et al. Activation of immediate early genes in relation to proliferation and apoptosis of enterocytes after ischemia-reperfusion injury of small intestine. Transplant Proc. 2002;34:983 pubmed
  27. Davis S, Bozon B, Laroche S. How necessary is the activation of the immediate early gene zif268 in synaptic plasticity and learning?. Behav Brain Res. 2003;142:17-30 pubmed
    The immediate early genes (IEGs) are activated rapidly and transiently in response to a multitude of stimuli...
  28. Dziema H, Oatis B, Butcher G, Yates R, Hoyt K, Obrietan K. The ERK/MAP kinase pathway couples light to immediate-early gene expression in the suprachiasmatic nucleus. Eur J Neurosci. 2003;17:1617-27 pubmed
    ..MAPK pathway-dependent gene expression in the SCN may result, in part, from stimulation of CRE-dependent transcription. ..
  29. Zhang D, Zhang L, Lou D, Nakabeppu Y, Zhang J, Xu M. The dopamine D1 receptor is a critical mediator for cocaine-induced gene expression. J Neurochem. 2002;82:1453-64 pubmed
    ..To test this possibility, we systematically compared the expression of the fos and Jun family immediate early genes in the nucleus accumbens and caudoputamen in D1 receptor mutant and wild-type control mice after acute and ..
  30. Montag Sallaz M, Buonviso N. Altered odor-induced expression of c-fos and arg 3.1 immediate early genes in the olfactory system after familiarization with an odor. J Neurobiol. 2002;52:61-72 pubmed
  31. Yoshimura N, Kikuchi T, Kuroiwa S, Gaun S. Differential temporal and spatial expression of immediate early genes in retinal neurons after ischemia-reperfusion injury. Invest Ophthalmol Vis Sci. 2003;44:2211-20 pubmed
    ..Temporal and spatial expression changes of immediate early genes and cell-cycle-related genes were studied by using real-time polymerase chain reaction (PCR) and ..
  32. Gerhauser I, Ulrich R, Alldinger S, Baumgartner W. Induction of activator protein-1 and nuclear factor-kappaB as a prerequisite for disease development in susceptible SJL/J mice after theiler murine encephalomyelitis. J Neuropathol Exp Neurol. 2007;66:809-18 pubmed
    ..In the late phase, the formation of JUN/JUN homodimers in intralesional astrocytes might contribute to the sustained release of proinflammatory cytokines, thereby promoting disease progression. ..
  33. Berezhnoĭ A, Vaĭnson A, Kasatkina N, Khokhlova O, Ostrovskaia A, Volodina E, et al. [High-dose gamma-irradiation enhance expression of transgene under control of immediate-early CMV promoter in stably transfected tumor cells]. Mol Biol (Mosk). 2008;42:501-9 pubmed
    ..Overall, our results supports using of 100 Gr of gamma-irradiation as the optimal dose for whole-cell anticancer vaccine inactivation. ..
  34. Bak X, Yang J, Wang S. Baculovirus-transduced bone marrow mesenchymal stem cells for systemic cancer therapy. Cancer Gene Ther. 2010;17:721-9 pubmed publisher
    ..Our findings suggest that baculoviral transduction of MSCs is an attractive option to generate targeting vehicles for systemic cancer therapy. ..
  35. Vilpoux C, Warnault V, Pierrefiche O, Daoust M, Naassila M. Ethanol-sensitive brain regions in rat and mouse: a cartographic review, using immediate early gene expression. Alcohol Clin Exp Res. 2009;33:945-69 pubmed publisher
    ..Ethanol-dependence is a chronic pathology with repeated cycles of withdrawal, craving, and relapse. Specific molecular and cellular mechanisms underlie these transition stages...
  36. Ramirez Amaya V, Vazdarjanova A, Mikhael D, Rosi S, Worley P, Barnes C. Spatial exploration-induced Arc mRNA and protein expression: evidence for selective, network-specific reactivation. J Neurosci. 2005;25:1761-8 pubmed
    ..This is the first demonstration of network-selective translational events consequent to spatial behavior and suggests a role for immediate-early genes in circuit-specific, late-phase synaptic biology. ..
  37. Satoh J, Nanri Y, Tabunoki H, Yamamura T. Microarray analysis identifies a set of CXCR3 and CCR2 ligand chemokines as early IFNbeta-responsive genes in peripheral blood lymphocytes in vitro: an implication for IFNbeta-related adverse effects in multiple sclerosis. BMC Neurol. 2006;6:18 pubmed
    ..IFNbeta immediately induces a burst of gene expression of proinflammatory chemokines in vitro that have potential relevance to IFNbeta-related early adverse effects in MS patients in vivo. ..
  38. Reisch A, Illing R, Laszig R. Immediate early gene expression invoked by electrical intracochlear stimulation in some but not all types of neurons in the rat auditory brainstem. Exp Neurol. 2007;208:193-206 pubmed
    ..Among the indicators for the initiation of neuronal remodeling is the expression of immediate early genes (IEGs). The IEGs c-fos and egr-1 encode transcription factors...
  39. Farivar R, Zangenehpour S, Chaudhuri A. Cellular-resolution activity mapping of the brain using immediate-early gene expression. Front Biosci. 2004;9:104-9 pubmed
    ..Current developments highlight the future prospects of cellular-resolution functional activity mapping of the brain. ..
  40. Thalhauser C, Komarova N. Specificity and robustness of the mammalian MAPK-IEG network. Biophys J. 2009;96:3471-82 pubmed publisher
    ..Finally, we quantify the role of the RKIP protein in shaping the signal, and propose a novel mechanism of its involvement in cancer metastasis. ..
  41. Nawa A, Luo C, Zhang L, Ushjima Y, Ishida D, Kamakura M, et al. Non-engineered, naturally oncolytic herpes simplex virus HSV1 HF-10: applications for cancer gene therapy. Curr Gene Ther. 2008;8:208-21 pubmed
    ..We also discuss the preclinical and clinical studies of HF-10, a non-engineered oncolytic HSV-1 virus, and its potential for use in cancer gene therapy. ..
  42. Pace T, Gaylord R, Topczewski F, Girotti M, Rubin B, Spencer R. Immediate-early gene induction in hippocampus and cortex as a result of novel experience is not directly related to the stressfulness of that experience. Eur J Neurosci. 2005;22:1679-90 pubmed
  43. He F, Ho Y, Yu L, Kwang J. WSSV ie1 promoter is more efficient than CMV promoter to express H5 hemagglutinin from influenza virus in baculovirus as a chicken vaccine. BMC Microbiol. 2008;8:238 pubmed publisher
    ..The worldwide outbreak of influenza A (H5N1) viruses among poultry species and humans highlighted the need to develop efficacious and safe vaccines based on efficient and scaleable production...
  44. Fedirko N, Gerasimenko J, Tepikin A, Gerasimenko O. Regulation of early response genes in pancreatic acinar cells: external calcium and nuclear calcium signalling aspects. Acta Physiol (Oxf). 2009;195:51-60 pubmed publisher
    ..investigated the possible consequences of nuclear calcium signals: the role of Ca(2+) in the regulation of immediate early genes (IEG): c-fos, c-myc and c-jun in pancreatic acinar cells...
  45. Terao A, Wisor J, Peyron C, Apte Deshpande A, Wurts S, Edgar D, et al. Gene expression in the rat brain during sleep deprivation and recovery sleep: an Affymetrix GeneChip study. Neuroscience. 2006;137:593-605 pubmed
  46. Resch W, Moss B. The conserved poxvirus L3 virion protein is required for transcription of vaccinia virus early genes. J Virol. 2005;79:14719-29 pubmed
  47. Burmeister S, Fernald R. Evolutionary conservation of the egr-1 immediate-early gene response in a teleost. J Comp Neurol. 2005;481:220-32 pubmed
    ..We conclude that the egr-1 immediate-early gene response is evolutionarily conserved and will, therefore, be useful for identifying functional neural responses in nontraditional model species. ..
  48. Hurley M, Jenner P. What has been learnt from study of dopamine receptors in Parkinson's disease?. Pharmacol Ther. 2006;111:715-28 pubmed
  49. Tanaka J. [Mechanisms of infection and replication of betaherpesviruses]. Nihon Rinsho. 2006;64 Suppl 3:400-3 pubmed
  50. Savard M, Barbaz D, Belanger S, Muller Esterl W, Bkaily G, D Orléans Juste P, et al. Expression of endogenous nuclear bradykinin B2 receptors mediating signaling in immediate early gene activation. J Cell Physiol. 2008;216:234-44 pubmed publisher
    ..This study discloses a previously undescribed mechanism in BK-induced transcriptional events, via intracrine B2R-mediated signaling, occurring in rat autologous hepatic cells. ..
  51. Yamada M, Yamada M, Takahashi K, Maruyama Y. [Pharmacogenomics and future development of novel antidepressants]. Nihon Yakurigaku Zasshi. 2006;128:19-22 pubmed
  52. Keller M, Wu A, Andrews J, McGonagill P, Tibesar E, Meier J. Reversal of human cytomegalovirus major immediate-early enhancer/promoter silencing in quiescently infected cells via the cyclic AMP signaling pathway. J Virol. 2007;81:6669-81 pubmed
    ..We conclude that stimulation of the cAMP/PKA signaling pathway drives CRE-dependent MIE enhancer/promoter activation in quiescently infected cells, thus exposing a potential mode of regulation in HCMV reactivation. ..
  53. Wirtshafter D. Rotation and immediate-early gene expression in rats treated with the atypical D1 dopamine agonist SKF 83822. Pharmacol Biochem Behav. 2007;86:505-10 pubmed
    ..Although PLC may be involved in many effects mediated through dopamine D1 receptors, these results suggest that direct activation of PLC is not necessary for the induction of either rotation or IEG expression in dopamine depleted rats. ..