Abstract
A cohort of the serum and growth factor regulated immediate-early gene set is induced with slower kinetics than c-fos. Two of the first immediate-early genes characterized as such, c-myc and JE, are contained within this subset. cis-acting genomic elements mediating induction of the slower responding subset of immediate-early genes have never been characterized. Herein we characterize two widely separated genomic elements which are together essential for induction of the murine JE gene by platelet-derived growth factor, serum, interleukin-1, and double-stranded RNA. One of these elements is novel in several regards. It is a 7-mer, TTTTGTA, found in the proximal 3' sequences downstream of the JE stop codon. The 3' element is position dependent and orientation independent. It does not function in polyadenylation, splicing, or destabilization of the JE transcript. Copies of the 7-mer or its inverse are found at comparable 3' sites in 25 immediate-early genes that encode transcription factors or cytokines. Given its general occurrence, the 7-mer may be a required cis-acting control element mediating induction of the immediate-early gene set.
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Selected References
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- Akira S., Isshiki H., Sugita T., Tanabe O., Kinoshita S., Nishio Y., Nakajima T., Hirano T., Kishimoto T. A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J. 1990 Jun;9(6):1897–1906. doi: 10.1002/j.1460-2075.1990.tb08316.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Anisowicz A., Bardwell L., Sager R. Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7188–7192. doi: 10.1073/pnas.84.20.7188. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berkowitz L. A., Riabowol K. T., Gilman M. Z. Multiple sequence elements of a single functional class are required for cyclic AMP responsiveness of the mouse c-fos promoter. Mol Cell Biol. 1989 Oct;9(10):4272–4281. doi: 10.1128/mcb.9.10.4272. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Birnstiel M. L., Busslinger M., Strub K. Transcription termination and 3' processing: the end is in site! Cell. 1985 Jun;41(2):349–359. doi: 10.1016/s0092-8674(85)80007-6. [DOI] [PubMed] [Google Scholar]
- Brown P. H., Tiley L. S., Cullen B. R. Effect of RNA secondary structure on polyadenylation site selection. Genes Dev. 1991 Jul;5(7):1277–1284. doi: 10.1101/gad.5.7.1277. [DOI] [PubMed] [Google Scholar]
- 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]
- Christy B. A., Lau L. F., Nathans D. A gene activated in mouse 3T3 cells by serum growth factors encodes a protein with "zinc finger" sequences. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7857–7861. doi: 10.1073/pnas.85.21.7857. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Christy B., Nathans D. Functional serum response elements upstream of the growth factor-inducible gene zif268. Mol Cell Biol. 1989 Nov;9(11):4889–4895. doi: 10.1128/mcb.9.11.4889. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Claesson-Welsh L., Eriksson A., Westermark B., Heldin C. H. cDNA cloning and expression of the human A-type platelet-derived growth factor (PDGF) receptor establishes structural similarity to the B-type PDGF receptor. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4917–4921. doi: 10.1073/pnas.86.13.4917. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Cochran B. H., Zullo J., Verma I. M., Stiles C. D. Expression of the c-fos gene and of an fos-related gene is stimulated by platelet-derived growth factor. Science. 1984 Nov 30;226(4678):1080–1082. doi: 10.1126/science.6093261. [DOI] [PubMed] [Google Scholar]
- Cohen D. R., Curran T. fra-1: a serum-inducible, cellular immediate-early gene that encodes a fos-related antigen. Mol Cell Biol. 1988 May;8(5):2063–2069. doi: 10.1128/mcb.8.5.2063. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crosby S. D., Puetz J. J., Simburger K. S., Fahrner T. J., Milbrandt J. The early response gene NGFI-C encodes a zinc finger transcriptional activator and is a member of the GCGGGGGCG (GSG) element-binding protein family. Mol Cell Biol. 1991 Aug;11(8):3835–3841. doi: 10.1128/mcb.11.8.3835. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fisch T. M., Prywes R., Simon M. C., Roeder R. G. Multiple sequence elements in the c-fos promoter mediate induction by cAMP. Genes Dev. 1989 Feb;3(2):198–211. doi: 10.1101/gad.3.2.198. [DOI] [PubMed] [Google Scholar]
- Gilman M. Z. The c-fos serum response element responds to protein kinase C-dependent and -independent signals but not to cyclic AMP. Genes Dev. 1988 Apr;2(4):394–402. doi: 10.1101/gad.2.4.394. [DOI] [PubMed] [Google Scholar]
- Goodbourn S., Burstein H., Maniatis T. The human beta-interferon gene enhancer is under negative control. Cell. 1986 May 23;45(4):601–610. doi: 10.1016/0092-8674(86)90292-8. [DOI] [PubMed] [Google Scholar]
- Goodbourn S., Zinn K., Maniatis T. Human beta-interferon gene expression is regulated by an inducible enhancer element. Cell. 1985 Jun;41(2):509–520. doi: 10.1016/s0092-8674(85)80024-6. [DOI] [PubMed] [Google Scholar]
- Graham R., Gilman M. Distinct protein targets for signals acting at the c-fos serum response element. Science. 1991 Jan 11;251(4990):189–192. doi: 10.1126/science.1898992. [DOI] [PubMed] [Google Scholar]
- Greenberg M. E., Siegfried Z., Ziff E. B. Mutation of the c-fos gene dyad symmetry element inhibits serum inducibility of transcription in vivo and the nuclear regulatory factor binding in vitro. Mol Cell Biol. 1987 Mar;7(3):1217–1225. doi: 10.1128/mcb.7.3.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
- Hall D. J., Brownlee C., Stiles C. D. Interleukin-1 is a potent regulator of JE and KC gene expression in quiescent BALB/c fibroblasts. J Cell Physiol. 1989 Oct;141(1):154–159. doi: 10.1002/jcp.1041410123. [DOI] [PubMed] [Google Scholar]
- Hall D. J., Jones S. D., Kaplan D. R., Whitman M., Rollins B. J., Stiles C. D. Evidence for a novel signal transduction pathway activated by platelet-derived growth factor and by double-stranded RNA. Mol Cell Biol. 1989 Apr;9(4):1705–1713. doi: 10.1128/mcb.9.4.1705. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hall D. J., Stiles C. D. Platelet-derived growth factor-inducible genes respond differentially to at least two distinct intracellular second messengers. J Biol Chem. 1987 Nov 5;262(31):15302–15308. [PubMed] [Google Scholar]
- Hart C. E., Forstrom J. W., Kelly J. D., Seifert R. A., Smith R. A., Ross R., Murray M. J., Bowen-Pope D. F. Two classes of PDGF receptor recognize different isoforms of PDGF. Science. 1988 Jun 10;240(4858):1529–1531. doi: 10.1126/science.2836952. [DOI] [PubMed] [Google Scholar]
- Hazel T. G., Nathans D., Lau L. F. A gene inducible by serum growth factors encodes a member of the steroid and thyroid hormone receptor superfamily. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8444–8448. doi: 10.1073/pnas.85.22.8444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kawasaki E. S., Ladner M. B., Wang A. M., Van Arsdell J., Warren M. K., Coyne M. Y., Schweickart V. L., Lee M. T., Wilson K. J., Boosman A. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science. 1985 Oct 18;230(4723):291–296. doi: 10.1126/science.2996129. [DOI] [PubMed] [Google Scholar]
- Kelly K., Cochran B. H., Stiles C. D., Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. doi: 10.1016/0092-8674(83)90092-2. [DOI] [PubMed] [Google Scholar]
- Kruijer W., Cooper J. A., Hunter T., Verma I. M. Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature. 1984 Dec 20;312(5996):711–716. doi: 10.1038/312711a0. [DOI] [PubMed] [Google Scholar]
- Lenardo M. J., Fan C. M., Maniatis T., Baltimore D. The involvement of NF-kappa B in beta-interferon gene regulation reveals its role as widely inducible mediator of signal transduction. Cell. 1989 Apr 21;57(2):287–294. doi: 10.1016/0092-8674(89)90966-5. [DOI] [PubMed] [Google Scholar]
- Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Misra R. P., Rivera V. M., Wang J. M., Fan P. D., Greenberg M. E. The serum response factor is extensively modified by phosphorylation following its synthesis in serum-stimulated fibroblasts. Mol Cell Biol. 1991 Sep;11(9):4545–4554. doi: 10.1128/mcb.11.9.4545. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müller R., Bravo R., Burckhardt J., Curran T. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature. 1984 Dec 20;312(5996):716–720. doi: 10.1038/312716a0. [DOI] [PubMed] [Google Scholar]
- Norman C., Runswick M., Pollock R., Treisman R. Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element. Cell. 1988 Dec 23;55(6):989–1003. doi: 10.1016/0092-8674(88)90244-9. [DOI] [PubMed] [Google Scholar]
- Olashaw N. E., Kusmik W., Daniel T. O., Pledger W. J. Biochemical and functional discrimination of platelet-derived growth factor alpha and beta receptors in BALB/c-3T3 cells. J Biol Chem. 1991 Jun 5;266(16):10234–10240. [PubMed] [Google Scholar]
- Oquendo P., Alberta J., Wen D. Z., Graycar J. L., Derynck R., Stiles C. D. The platelet-derived growth factor-inducible KC gene encodes a secretory protein related to platelet alpha-granule proteins. J Biol Chem. 1989 Mar 5;264(7):4133–4137. [PubMed] [Google Scholar]
- Pledger W. J., Stiles C. D., Antoniades H. N., Scher C. D. Induction of DNA synthesis in BALB/c 3T3 cells by serum components: reevaluation of the commitment process. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4481–4485. doi: 10.1073/pnas.74.10.4481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pollock R., Treisman R. Human SRF-related proteins: DNA-binding properties and potential regulatory targets. Genes Dev. 1991 Dec;5(12A):2327–2341. doi: 10.1101/gad.5.12a.2327. [DOI] [PubMed] [Google Scholar]
- Prywes R., Roeder R. G. Inducible binding of a factor to the c-fos enhancer. Cell. 1986 Dec 5;47(5):777–784. doi: 10.1016/0092-8674(86)90520-9. [DOI] [PubMed] [Google Scholar]
- Prywes R., Roeder R. G. Purification of the c-fos enhancer-binding protein. Mol Cell Biol. 1987 Oct;7(10):3482–3489. doi: 10.1128/mcb.7.10.3482. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Qureshi S. A., Cao X. M., Sukhatme V. P., Foster D. A. v-Src activates mitogen-responsive transcription factor Egr-1 via serum response elements. J Biol Chem. 1991 Jun 15;266(17):10802–10806. [PubMed] [Google Scholar]
- Rollins B. J., Morrison E. D., Stiles C. D. Cloning and expression of JE, a gene inducible by platelet-derived growth factor and whose product has cytokine-like properties. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3738–3742. doi: 10.1073/pnas.85.11.3738. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rollins B. J., Stier P., Ernst T., Wong G. G. The human homolog of the JE gene encodes a monocyte secretory protein. Mol Cell Biol. 1989 Nov;9(11):4687–4695. doi: 10.1128/mcb.9.11.4687. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Sacca R., Cochran B. H. Identification of a PDGF-responsive element in the murine c-myc gene. Oncogene. 1990 Oct;5(10):1499–1505. [PubMed] [Google Scholar]
- 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]
- Sassone-Corsi P., Visvader J., Ferland L., Mellon P. L., Verma I. M. Induction of proto-oncogene fos transcription through the adenylate cyclase pathway: characterization of a cAMP-responsive element. Genes Dev. 1988 Dec;2(12A):1529–1538. doi: 10.1101/gad.2.12a.1529. [DOI] [PubMed] [Google Scholar]
- Sen R., Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986 Aug 29;46(5):705–716. doi: 10.1016/0092-8674(86)90346-6. [DOI] [PubMed] [Google Scholar]
- Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
- Shyu A. B., Greenberg M. E., Belasco J. G. The c-fos transcript is targeted for rapid decay by two distinct mRNA degradation pathways. Genes Dev. 1989 Jan;3(1):60–72. doi: 10.1101/gad.3.1.60. [DOI] [PubMed] [Google Scholar]
- Spencer C. A., Groudine M. Control of c-myc regulation in normal and neoplastic cells. Adv Cancer Res. 1991;56:1–48. doi: 10.1016/s0065-230x(08)60476-5. [DOI] [PubMed] [Google Scholar]
- Treisman R. Identification and purification of a polypeptide that binds to the c-fos serum response element. EMBO J. 1987 Sep;6(9):2711–2717. doi: 10.1002/j.1460-2075.1987.tb02564.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Treisman R. Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors. Cell. 1986 Aug 15;46(4):567–574. doi: 10.1016/0092-8674(86)90882-2. [DOI] [PubMed] [Google Scholar]
- Treisman R. The SRE: a growth factor responsive transcriptional regulator. Semin Cancer Biol. 1990 Feb;1(1):47–58. [PubMed] [Google Scholar]
- Treisman R. Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5' element and c-fos 3' sequences. Cell. 1985 Oct;42(3):889–902. doi: 10.1016/0092-8674(85)90285-5. [DOI] [PubMed] [Google Scholar]
- Wagner B. J., Hayes T. E., Hoban C. J., Cochran B. H. The SIF binding element confers sis/PDGF inducibility onto the c-fos promoter. EMBO J. 1990 Dec;9(13):4477–4484. doi: 10.1002/j.1460-2075.1990.tb07898.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wasylyk B., Wasylyk C., Flores P., Begue A., Leprince D., Stehelin D. The c-ets proto-oncogenes encode transcription factors that cooperate with c-Fos and c-Jun for transcriptional activation. Nature. 1990 Jul 12;346(6280):191–193. doi: 10.1038/346191a0. [DOI] [PubMed] [Google Scholar]
- Williams T. M., Moolten D., Burlein J., Romano J., Bhaerman R., Godillot A., Mellon M., Rauscher F. J., 3rd, Kant J. A. Identification of a zinc finger protein that inhibits IL-2 gene expression. Science. 1991 Dec 20;254(5039):1791–1794. doi: 10.1126/science.1840704. [DOI] [PubMed] [Google Scholar]
- Wolf F. W., Marks R. M., Sarma V., Byers M. G., Katz R. W., Shows T. B., Dixit V. M. Characterization of a novel tumor necrosis factor-alpha-induced endothelial primary response gene. J Biol Chem. 1992 Jan 15;267(2):1317–1326. [PubMed] [Google Scholar]
- Zerial M., Toschi L., Ryseck R. P., Schuermann M., Müller R., Bravo R. The product of a novel growth factor activated gene, fos B, interacts with JUN proteins enhancing their DNA binding activity. EMBO J. 1989 Mar;8(3):805–813. doi: 10.1002/j.1460-2075.1989.tb03441.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zinn K., DiMaio D., Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. doi: 10.1016/0092-8674(83)90544-5. [DOI] [PubMed] [Google Scholar]
- Zullo J. N., Cochran B. H., Huang A. S., Stiles C. D. Platelet-derived growth factor and double-stranded ribonucleic acids stimulate expression of the same genes in 3T3 cells. Cell. 1985 Dec;43(3 Pt 2):793–800. doi: 10.1016/0092-8674(85)90252-1. [DOI] [PubMed] [Google Scholar]
- de Belle I., Walker P. R., Smith I. C., Sikorska M. Identification of a multiprotein complex interacting with the c-fos serum response element. Mol Cell Biol. 1991 May;11(5):2752–2759. doi: 10.1128/mcb.11.5.2752. [DOI] [PMC free article] [PubMed] [Google Scholar]