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Gene Review

EGR2  -  early growth response 2

Homo sapiens

Synonyms: AT591, CMT1D, CMT4E, E3 SUMO-protein ligase EGR2, EGR-2, ...
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Disease relevance of EGR2


Psychiatry related information on EGR2

  • Microsatellite marker D10S1225, associated with Alzheimer's disease, non-syndromic congenital retinal non-attachment (NCRNA) and non-syndromic autosomal recessive persistent hyperplastic primary vitreous (arPHPV), was located within the TRIP8-EGR2 locus [6].

High impact information on EGR2

  • In support of this hypothesis, we have identified one recessive and two dominant missense mutations in EGR2 (within regions encoding conserved functional domains) in patients with congenital hypomyelinating neuropathy (CHN) and a family with Charcot-Marie-Tooth type 1 (CMT1) [7].
  • The early growth response 2 gene (EGR2) is part of a multigene family encoding Cys2His2 type zinc-finger proteins and may play a role in the regulation of cellular proliferation [7].
  • Egr2(-/-) mice display disrupted hindbrain segmentation and development, and a block of Schwann-cell differentiation at an early stage [7].
  • We hypothesized that Egr2 may be a transcription factor affecting late myelin genes and that human myelinopathies of the PNS may result from mutations in EGR2 [7].
  • Stable expression of Egr2 is specifically associated with the onset of myelination in the peripheral nervous system (PNS) [7].

Biological context of EGR2

  • Strikingly, the deduced amino acid sequences of human EGR2 and mouse Egr-1 are 92% identical in the zinc finger region but show no similarity elsewhere [8].
  • EGR2 maps to human chromosome 10 at bands q21-22 [8].
  • Using adenovirus-mediated gene transfer to 39 cancer cell lines, we found that EGR2 could induce apoptosis in a large proportion of these lines by altering the permeability of mitochondrial membranes, releasing cytochrome c and activating caspase-3, -8, and -9 [9].
  • Colony-formation assays using plasmid clones designed to express each gene indicated that EGR2 and BPOZ were able to suppress growth of cancer cells significantly; in particular, cancer-cell lines stably expressing BPOZ grew more slowly than control cells containing mock vector [10].
  • Anti-sense oligonucleotides for BPOZ or EGR2 effectively inhibited their expression, and cell growth was accelerated [10].

Anatomical context of EGR2

  • These data suggest that interaction between the Cx32 P2 promoter, SOX10, and EGR2 highlight a mechanism of peripheral nerve dysfunction [11].
  • Although the expression of EGR2 mutants inhibits the transactivation of myelin gene promoters, the exact molecular mechanism by which these mutations cause the alteration of the myelination process is still unknown [12].
  • Furthermore, in contrast to patients with typical DSN, patients with the EGR2 R359W mutation have more respiratory compromise and cranial nerve involvement [13].
  • They were transiently co-transfected with NGFI-A, NGFI-C, Krox-20 and NGFI-B expression vectors in NG108-15, SN6 and COS-1 cells [14].
  • Krox 20, expressed in myelinating but not promyelinating Schwann cells, is absolutely required for this transition, and myelination cannot occur in its absence [15].

Associations of EGR2 with chemical compounds

  • EGR1 and EGR2 increased IL-3 promoter activity when the transfected cells were stimulated with phorbol-12-myristate-13-acetate and A23187 [16].
  • Finally, we demonstrate that dexamethasone, an inhibitor of monocytic differentiation, blocks the associated increases in EGR-1 and EGR-2 expression [4].
  • The effect of coincubation with dibutyryl-cAMP (dBcAMP) was assessed in an attempt to prevent the colchicine-induced increase in PDGF(B) mRNA. dBcAMP alone resulted in no increase in PDGF(B) mRNA or alteration in TGF-beta mRNA but resulted in a reduction in EGR2 mRNA [17].
  • PAF (10(-7) M) increased c-fos and EGR2 mRNA levels in cells suspended in Ca(2+)-containing medium by 6-10-fold [18].
  • These neurons also showed persistent cyclic adenosine monophosphate response element binding protein (CREB) activation and nuclear translocation of EGR-2 and c-fos proteins [19].

Physical interactions of EGR2


Regulatory relationships of EGR2

  • Known inducers of Mpz expression such as forskolin and insulin-like growth factor-1 also activate the element in an Egr2-dependent manner [22].

Other interactions of EGR2

  • Our study shows that this factor, in synergy with EGR2, strongly activates Cx32 expression in vitro by directly binding to its promoter [23].
  • Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway [10].
  • A second group contains the regulators of myelin gene transcription EGR2/Krox20 and SOX10 [24].
  • No mutation was detected in genes PMP22, EGR2 and LITAF among the remaining nine (28.1%) CMT1 patients [25].
  • Dominant and recessive mutations in EGR2 are associated with peripheral myelinopathies, such as Charcot-Marie-Tooth disease type 1, Dejerine-Sottas syndrome, and congenital hypomyelinating neuropathy [26].

Analytical, diagnostic and therapeutic context of EGR2


  1. Novel missense mutation in the early growth response 2 gene associated with Dejerine-Sottas syndrome phenotype. Timmerman, V., De Jonghe, P., Ceuterick, C., De Vriendt, E., Löfgren, A., Nelis, E., Warner, L.E., Lupski, J.R., Martin, J.J., Van Broeckhoven, C. Neurology (1999) [Pubmed]
  2. Novel EGR2 mutation R359Q is associated with CMT type 1 and progressive scoliosis. Mikesová, E., Hühne, K., Rautenstrauss, B., Mazanec, R., Baránková, L., Vyhnálek, M., Horácek, O., Seeman, P. Neuromuscul. Disord. (2005) [Pubmed]
  3. Characterization of a subfamily of zinc finger genes expressed in human hematopoietic cell lines. Munaro, M., Petroni, D., Di Fazio, M., Comi, P., Ottolenghi, S. Cytotechnology. (1991) [Pubmed]
  4. Expression of the early growth response 1 and 2 zinc finger genes during induction of monocytic differentiation. Kharbanda, S., Nakamura, T., Stone, R., Hass, R., Bernstein, S., Datta, R., Sukhatme, V.P., Kufe, D. J. Clin. Invest. (1991) [Pubmed]
  5. Two missense mutations of EGR2 R359W and GJB1 V136A in a Charcot-Marie-Tooth disease family. Chung, K.W., Sunwoo, I.N., Kim, S.M., Park, K.D., Kim, W.K., Kim, T.S., Koo, H., Cho, M., Lee, J., Choi, B.O. Neurogenetics (2005) [Pubmed]
  6. Identification and characterization of TRIP8 gene in silico. Katoh, M., Katoh, M. Int. J. Mol. Med. (2003) [Pubmed]
  7. Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. Warner, L.E., Mancias, P., Butler, I.J., McDonald, C.M., Keppen, L., Koob, K.G., Lupski, J.R. Nat. Genet. (1998) [Pubmed]
  8. Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with "zinc-binding finger" structure. Joseph, L.J., Le Beau, M.M., Jamieson, G.A., Acharya, S., Shows, T.B., Rowley, J.D., Sukhatme, V.P. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  9. EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK. Unoki, M., Nakamura, Y. Oncogene (2003) [Pubmed]
  10. Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway. Unoki, M., Nakamura, Y. Oncogene (2001) [Pubmed]
  11. Connexin 32 promoter P2 mutations: a mechanism of peripheral nerve dysfunction. Houlden, H., Girard, M., Cockerell, C., Ingram, D., Wood, N.W., Goossens, M., Walker, R.W., Reilly, M.M. Ann. Neurol. (2004) [Pubmed]
  12. Different consequences of EGR2 mutants on the transactivation of human Cx32 promoter. Musso, M., Balestra, P., Taroni, F., Bellone, E., Mandich, P. Neurobiol. Dis. (2003) [Pubmed]
  13. EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy. Boerkoel, C.F., Takashima, H., Bacino, C.A., Daentl, D., Lupski, J.R. Neurogenetics (2001) [Pubmed]
  14. Transcriptional activation of human choline acetyltransferase by AP2- and NGF-induced factors. Quirin-Stricker, C., Mauvais, C., Schmitt, M. Brain Res. Mol. Brain Res. (1997) [Pubmed]
  15. Regulation of myelin-specific gene expression. Relevance to CMT1. Kamholz, J., Awatramani, R., Menichella, D., Jiang, H., Xu, W., Shy, M. Ann. N. Y. Acad. Sci. (1999) [Pubmed]
  16. Molecular cloning of a novel human cDNA encoding a zinc finger protein that binds to the interleukin-3 promoter. Koyano-Nakagawa, N., Nishida, J., Baldwin, D., Arai, K., Yokota, T. Mol. Cell. Biol. (1994) [Pubmed]
  17. Modulation of platelet-derived growth factor B mRNA abundance in macrophages by colchicine and dibutyryl-cAMP. Wangoo, A., Haynes, A.R., Sutcliffe, S.P., Sorooshian, M., Shaw, R.J. Mol. Pharmacol. (1992) [Pubmed]
  18. Role for Ca2+ in expression of cell cycle regulated genes in PAF-stimulated cells. Mazer, B.D., Domenico, J., Szepesi, A., Lucas, J.J., Gelfand, E.W. Journal of lipid mediators and cell signalling. (1994) [Pubmed]
  19. A common pattern of persistent gene activation in human neocortical epileptic foci. Rakhade, S.N., Yao, B., Ahmed, S., Asano, E., Beaumont, T.L., Shah, A.K., Draghici, S., Krauss, R., Chugani, H.T., Sood, S., Loeb, J.A. Ann. Neurol. (2005) [Pubmed]
  20. The D355V mutation decreases EGR2 binding to an element within the Cx32 promoter. Musso, M., Balestra, P., Bellone, E., Cassandrini, D., Di Maria, E., Doria, L.L., Grandis, M., Mancardi, G.L., Schenone, A., Levi, G., Ajmar, F., Mandich, P. Neurobiol. Dis. (2001) [Pubmed]
  21. In vivo detection of Egr2 binding to target genes during peripheral nerve myelination. Jang, S.W., LeBlanc, S.E., Roopra, A., Wrabetz, L., Svaren, J. J. Neurochem. (2006) [Pubmed]
  22. Direct regulation of myelin protein zero expression by the Egr2 transactivator. LeBlanc, S.E., Jang, S.W., Ward, R.M., Wrabetz, L., Svaren, J. J. Biol. Chem. (2006) [Pubmed]
  23. Human Connexin 32, a gap junction protein altered in the X-linked form of Charcot-Marie-Tooth disease, is directly regulated by the transcription factor SOX10. Bondurand, N., Girard, M., Pingault, V., Lemort, N., Dubourg, O., Goossens, M. Hum. Mol. Genet. (2001) [Pubmed]
  24. Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot-Marie-Tooth disease). Berger, P., Niemann, A., Suter, U. Glia (2006) [Pubmed]
  25. Mutation frequency for Charcot-Marie-Tooth disease type 1 in the Chinese population is similar to that in the global ethnic patients. Song, S., Zhang, Y., Chen, B., Zhang, Y., Wang, M., Wang, Y., Yan, M., Zou, J., Huang, Y., Zhong, N. Genet. Med. (2006) [Pubmed]
  26. Search for mutations in the EGR2 corepressor proteins, NAB1 and NAB2, in human peripheral neuropathies. Venken, K., Di Maria, E., Bellone, E., Balestra, P., Cassandrini, D., Mandich, P., De Jonghe, P., Timmerman, V., Svaren, J. Neurogenetics (2002) [Pubmed]
  27. Activity and injury-dependent expression of inducible transcription factors, growth factors and apoptosis-related genes within the central nervous system. Hughes, P.E., Alexi, T., Walton, M., Williams, C.E., Dragunow, M., Clark, R.G., Gluckman, P.D. Prog. Neurobiol. (1999) [Pubmed]
  28. Expression of early growth response genes in human prostate cancer. Eid, M.A., Kumar, M.V., Iczkowski, K.A., Bostwick, D.G., Tindall, D.J. Cancer Res. (1998) [Pubmed]
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