Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Oct;85(19):7164–7168. doi: 10.1073/pnas.85.19.7164

Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with "zinc-binding finger" structure.

L J Joseph 1, M M Le Beau 1, G A Jamieson Jr 1, S Acharya 1, T B Shows 1, J D Rowley 1, V P Sukhatme 1
PMCID: PMC282144  PMID: 3140236

Abstract

Early growth response gene-1 (Egr-1) is a mouse gene displaying fos-like induction kinetics in diverse cell types following mitogenic stimulation. Egr-1 encodes a protein with "zinc-binding finger" structure. Zinc fingers are a protein structural motif that serve as DNA-binding domains in several transcriptional regulatory proteins. Using low-stringency hybridization with an Egr-1 cDNA probe, we identified a distinct human cDNA (designated EGR2 for early growth response gene-2), which is coregulated with EGR1 by fibroblast and lymphocyte mitogens; however, several stimuli that induce Egr-1 mRNA in PC12 (rat pheochromocytoma) cells do not induce Egr-2 mRNA. The cDNA sequence predicts a protein of 406 amino acids, including three tandem zinc fingers of the Cys2-His2 class. 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. EGR2 maps to human chromosome 10 at bands q21-22. Structure-function analysis of EGR2 and EGR1 proteins should provide insight into the mechanisms linking signal transduction and transcriptional regulation of gene expression.

Full text

PDF
7164

Images in this article

7166Image
on p.7166
7166Image
on p.7166
7166Image
on p.7166
7166Image
on p.7166
7166Image
on p.7166
7166Image
on p.7166
7166Image
on p.7166
7166Image
on p.7166

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Almendral J. M., Sommer D., Macdonald-Bravo H., Burckhardt J., Perera J., Bravo R. Complexity of the early genetic response to growth factors in mouse fibroblasts. Mol Cell Biol. 1988 May;8(5):2140–2148. doi: 10.1128/mcb.8.5.2140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Angel P., Allegretto E. A., Okino S. T., Hattori K., Boyle W. J., Hunter T., Karin M. Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature. 1988 Mar 10;332(6160):166–171. doi: 10.1038/332166a0. [DOI] [PubMed] [Google Scholar]
  3. Berg J. M. Proposed structure for the zinc-binding domains from transcription factor IIIA and related proteins. Proc Natl Acad Sci U S A. 1988 Jan;85(1):99–102. doi: 10.1073/pnas.85.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bigner S. H., Mark J., Bullard D. E., Mahaley M. S., Jr, Bigner D. D. Chromosomal evolution in malignant human gliomas starts with specific and usually numerical deviations. Cancer Genet Cytogenet. 1986 Jun;22(2):121–135. doi: 10.1016/0165-4608(86)90172-x. [DOI] [PubMed] [Google Scholar]
  5. Bohmann D., Bos T. J., Admon A., Nishimura T., Vogt P. K., Tjian R. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science. 1987 Dec 4;238(4832):1386–1392. doi: 10.1126/science.2825349. [DOI] [PubMed] [Google Scholar]
  6. Brown R. S., Argos P. Fingers and helices. Nature. 1986 Nov 20;324(6094):215–215. doi: 10.1038/324215a0. [DOI] [PubMed] [Google Scholar]
  7. Chavrier P., Lemaire P., Revelant O., Bravo R., Charnay P. Characterization of a mouse multigene family that encodes zinc finger structures. Mol Cell Biol. 1988 Mar;8(3):1319–1326. doi: 10.1128/mcb.8.3.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chavrier P., Zerial M., Lemaire P., Almendral J., Bravo R., Charnay P. A gene encoding a protein with zinc fingers is activated during G0/G1 transition in cultured cells. EMBO J. 1988 Jan;7(1):29–35. doi: 10.1002/j.1460-2075.1988.tb02780.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cheley S., Anderson R. A reproducible microanalytical method for the detection of specific RNA sequences by dot-blot hybridization. Anal Biochem. 1984 Feb;137(1):15–19. doi: 10.1016/0003-2697(84)90339-7. [DOI] [PubMed] [Google Scholar]
  10. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  11. Chowdhury K., Deutsch U., Gruss P. A multigene family encoding several "finger" structures is present and differentially active in mammalian genomes. Cell. 1987 Mar 13;48(5):771–778. doi: 10.1016/0092-8674(87)90074-2. [DOI] [PubMed] [Google Scholar]
  12. Cochran B. H., Reffel A. C., Stiles C. D. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell. 1983 Jul;33(3):939–947. doi: 10.1016/0092-8674(83)90037-5. [DOI] [PubMed] [Google Scholar]
  13. Evans R. M., Hollenberg S. M. Zinc fingers: gilt by association. Cell. 1988 Jan 15;52(1):1–3. doi: 10.1016/0092-8674(88)90522-3. [DOI] [PubMed] [Google Scholar]
  14. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  15. Green S., Chambon P. Oestradiol induction of a glucocorticoid-responsive gene by a chimaeric receptor. Nature. 1987 Jan 1;325(6099):75–78. doi: 10.1038/325075a0. [DOI] [PubMed] [Google Scholar]
  16. Jamieson G. A., Jr, Etscheid B. G., Muldoon L. L., Villereal M. L. Effects of phorbol ester on mitogen and orthovanadate stimulated responses of cultured human fibroblasts. J Cell Physiol. 1988 Feb;134(2):220–228. doi: 10.1002/jcp.1041340207. [DOI] [PubMed] [Google Scholar]
  17. Kadonaga J. T., Carner K. R., Masiarz F. R., Tjian R. Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain. Cell. 1987 Dec 24;51(6):1079–1090. doi: 10.1016/0092-8674(87)90594-0. [DOI] [PubMed] [Google Scholar]
  18. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lau L. F., Nathans D. Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1182–1186. doi: 10.1073/pnas.84.5.1182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Le Beau M. M., Westbrook C. A., Diaz M. O., Rowley J. D. Evidence for two distinct c-src loci on human chromosomes 1 and 20. Nature. 1984 Nov 1;312(5989):70–71. doi: 10.1038/312070a0. [DOI] [PubMed] [Google Scholar]
  21. Lim R. W., Varnum B. C., Herschman H. R. Cloning of tetradecanoyl phorbol ester-induced 'primary response' sequences and their expression in density-arrested Swiss 3T3 cells and a TPA non-proliferative variant. Oncogene. 1987;1(3):263–270. [PubMed] [Google Scholar]
  22. Milbrandt J. A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor. Science. 1987 Nov 6;238(4828):797–799. doi: 10.1126/science.3672127. [DOI] [PubMed] [Google Scholar]
  23. Muldoon L. L., Jamieson G. A., Jr, Kao A. C., Palfrey H. C., Villereal M. L. Mitogen stimulation of Na+-H+ exchange: differential involvement of protein kinase C. Am J Physiol. 1987 Aug;253(2 Pt 1):C219–C229. doi: 10.1152/ajpcell.1987.253.2.C219. [DOI] [PubMed] [Google Scholar]
  24. Nagai K., Nakaseko Y., Nasmyth K., Rhodes D. Zinc-finger motifs expressed in E. coli and folded in vitro direct specific binding to DNA. Nature. 1988 Mar 17;332(6161):284–286. doi: 10.1038/332284a0. [DOI] [PubMed] [Google Scholar]
  25. Ryder K., Lau L. F., Nathans D. A gene activated by growth factors is related to the oncogene v-jun. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1487–1491. doi: 10.1073/pnas.85.5.1487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schuh R., Aicher W., Gaul U., Côté S., Preiss A., Maier D., Seifert E., Nauber U., Schröder C., Kemler R. A conserved family of nuclear proteins containing structural elements of the finger protein encoded by Krüppel, a Drosophila segmentation gene. Cell. 1986 Dec 26;47(6):1025–1032. doi: 10.1016/0092-8674(86)90817-2. [DOI] [PubMed] [Google Scholar]
  28. Shows T. B., Brown J. A., Haley L. L., Byers M. G., Eddy R. L., Cooper E. S., Goggin A. P. Assignment of the beta-glucuronidase structural gene to the pter leads to q22 region of chromosome 7 in man. Cytogenet Cell Genet. 1978;21(1-2):99–104. doi: 10.1159/000130882. [DOI] [PubMed] [Google Scholar]
  29. Shows T., Eddy R., Haley L., Byers M., Henry M., Fujita T., Matsui H., Taniguchi T. Interleukin 2 (IL2) is assigned to human chromosome 4. Somat Cell Mol Genet. 1984 May;10(3):315–318. doi: 10.1007/BF01535253. [DOI] [PubMed] [Google Scholar]
  30. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  31. Sukhatme V. P., Kartha S., Toback F. G., Taub R., Hoover R. G., Tsai-Morris C. H. A novel early growth response gene rapidly induced by fibroblast, epithelial cell and lymphocyte mitogens. Oncogene Res. 1987 Sep-Oct;1(4):343–355. [PubMed] [Google Scholar]
  32. Vrana K. E., Churchill M. E., Tullius T. D., Brown D. D. Mapping functional regions of transcription factor TFIIIA. Mol Cell Biol. 1988 Apr;8(4):1684–1696. doi: 10.1128/mcb.8.4.1684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wickens M., Stephenson P. Role of the conserved AAUAAA sequence: four AAUAAA point mutants prevent messenger RNA 3' end formation. Science. 1984 Nov 30;226(4678):1045–1051. doi: 10.1126/science.6208611. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES