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. 1995 Jun;15(6):2907–2915. doi: 10.1128/mcb.15.6.2907

Regulatory role of MEF2D in serum induction of the c-jun promoter.

T H Han 1, R Prywes 1
PMCID: PMC230521  PMID: 7760790

Abstract

Serum induction of c-jun expression in HeLa cells requires a MEF2 site at -59 in the c-jun promoter. MEF2 sites, found in many muscle-specific enhancers, are bound by a family of transcription factors, MEF2A through -D, which are related to serum response factor in their DNA binding domains. We have found that MEF2D is the predominant protein in HeLa cells that binds to the c-jun MEF2 site. Serum induction of a MEF2 reporter gene was not observed in a line of NIH 3T3 cells which contain low MEF2 site binding activity. Transfection of MEF2D into NIH 3T3 cells reconstituted serum induction, demonstrating that MEF2D is required for the serum response. Deletion analysis of MEF2D showed that its DNA binding domain, when fused to a heterologous transcriptional activation domain, was sufficient for serum induction of a MEF2 reporter gene. This is the domain homologous to that in the serum response factor which is required for serum induction of the c-fos serum response element, suggesting that serum regulation of c-fos and c-jun may share a common mechanism.

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Selected References

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  1. Angel P., Hattori K., Smeal T., Karin M. The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1. Cell. 1988 Dec 2;55(5):875–885. doi: 10.1016/0092-8674(88)90143-2. [DOI] [PubMed] [Google Scholar]
  2. Braun T., Tannich E., Buschhausen-Denker G., Arnold H. H. Promoter upstream elements of the chicken cardiac myosin light-chain 2-A gene interact with trans-acting regulatory factors for muscle-specific transcription. Mol Cell Biol. 1989 Jun;9(6):2513–2525. doi: 10.1128/mcb.9.6.2513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Breitbart R. E., Liang C. S., Smoot L. B., Laheru D. A., Mahdavi V., Nadal-Ginard B. A fourth human MEF2 transcription factor, hMEF2D, is an early marker of the myogenic lineage. Development. 1993 Aug;118(4):1095–1106. doi: 10.1242/dev.118.4.1095. [DOI] [PubMed] [Google Scholar]
  4. Chambers A. E., Logan M., Kotecha S., Towers N., Sparrow D., Mohun T. J. The RSRF/MEF2 protein SL1 regulates cardiac muscle-specific transcription of a myosin light-chain gene in Xenopus embryos. Genes Dev. 1994 Jun 1;8(11):1324–1334. doi: 10.1101/gad.8.11.1324. [DOI] [PubMed] [Google Scholar]
  5. Chen C. Y., Shyu A. B. Selective degradation of early-response-gene mRNAs: functional analyses of sequence features of the AU-rich elements. Mol Cell Biol. 1994 Dec;14(12):8471–8482. doi: 10.1128/mcb.14.12.8471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cheng T. C., Wallace M. C., Merlie J. P., Olson E. N. Separable regulatory elements governing myogenin transcription in mouse embryogenesis. Science. 1993 Jul 9;261(5118):215–218. doi: 10.1126/science.8392225. [DOI] [PubMed] [Google Scholar]
  7. Cserjesi P., Olson E. N. Myogenin induces the myocyte-specific enhancer binding factor MEF-2 independently of other muscle-specific gene products. Mol Cell Biol. 1991 Oct;11(10):4854–4862. doi: 10.1128/mcb.11.10.4854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fisch T. M., Prywes R., Roeder R. G. c-fos sequence necessary for basal expression and induction by epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore. Mol Cell Biol. 1987 Oct;7(10):3490–3502. doi: 10.1128/mcb.7.10.3490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Giovane A., Pintzas A., Maira S. M., Sobieszczuk P., Wasylyk B. Net, a new ets transcription factor that is activated by Ras. Genes Dev. 1994 Jul 1;8(13):1502–1513. doi: 10.1101/gad.8.13.1502. [DOI] [PubMed] [Google Scholar]
  10. Gossett L. A., Kelvin D. J., Sternberg E. A., Olson E. N. A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes. Mol Cell Biol. 1989 Nov;9(11):5022–5033. doi: 10.1128/mcb.9.11.5022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Han T. H., Lamph W. W., Prywes R. Mapping of epidermal growth factor-, serum-, and phorbol ester-responsive sequence elements in the c-jun promoter. Mol Cell Biol. 1992 Oct;12(10):4472–4477. doi: 10.1128/mcb.12.10.4472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hattori K., Angel P., Le Beau M. M., Karin M. Structure and chromosomal localization of the functional intronless human JUN protooncogene. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9148–9152. doi: 10.1073/pnas.85.23.9148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Herschman H. R. Primary response genes induced by growth factors and tumor promoters. Annu Rev Biochem. 1991;60:281–319. doi: 10.1146/annurev.bi.60.070191.001433. [DOI] [PubMed] [Google Scholar]
  14. Hill C. S., Wynne J., Treisman R. Serum-regulated transcription by serum response factor (SRF): a novel role for the DNA binding domain. EMBO J. 1994 Nov 15;13(22):5421–5432. doi: 10.1002/j.1460-2075.1994.tb06877.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Horlick R. A., Benfield P. A. The upstream muscle-specific enhancer of the rat muscle creatine kinase gene is composed of multiple elements. Mol Cell Biol. 1989 Jun;9(6):2396–2413. doi: 10.1128/mcb.9.6.2396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Horlick R. A., Hobson G. M., Patterson J. H., Mitchell M. T., Benfield P. A. Brain and muscle creatine kinase genes contain common TA-rich recognition protein-binding regulatory elements. Mol Cell Biol. 1990 Sep;10(9):4826–4836. doi: 10.1128/mcb.10.9.4826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Johansen F. E., Prywes R. Two pathways for serum regulation of the c-fos serum response element require specific sequence elements and a minimal domain of serum response factor. Mol Cell Biol. 1994 Sep;14(9):5920–5928. doi: 10.1128/mcb.14.9.5920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lamph W. W., Wamsley P., Sassone-Corsi P., Verma I. M. Induction of proto-oncogene JUN/AP-1 by serum and TPA. Nature. 1988 Aug 18;334(6183):629–631. doi: 10.1038/334629a0. [DOI] [PubMed] [Google Scholar]
  19. Lassar A. B., Davis R. L., Wright W. E., Kadesch T., Murre C., Voronova A., Baltimore D., Weintraub H. Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell. 1991 Jul 26;66(2):305–315. doi: 10.1016/0092-8674(91)90620-e. [DOI] [PubMed] [Google Scholar]
  20. Lopez M., Oettgen P., Akbarali Y., Dendorfer U., Libermann T. A. ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development. Mol Cell Biol. 1994 May;14(5):3292–3309. doi: 10.1128/mcb.14.5.3292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Manak J. R., de Bisschop N., Kris R. M., Prywes R. Casein kinase II enhances the DNA binding activity of serum response factor. Genes Dev. 1990 Jun;4(6):955–967. doi: 10.1101/gad.4.6.955. [DOI] [PubMed] [Google Scholar]
  22. Martin J. F., Miano J. M., Hustad C. M., Copeland N. G., Jenkins N. A., Olson E. N. A Mef2 gene that generates a muscle-specific isoform via alternative mRNA splicing. Mol Cell Biol. 1994 Mar;14(3):1647–1656. doi: 10.1128/mcb.14.3.1647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Martin J. F., Schwarz J. J., Olson E. N. Myocyte enhancer factor (MEF) 2C: a tissue-restricted member of the MEF-2 family of transcription factors. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5282–5286. doi: 10.1073/pnas.90.11.5282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. McDermott J. C., Cardoso M. C., Yu Y. T., Andres V., Leifer D., Krainc D., Lipton S. A., Nadal-Ginard B. hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors. Mol Cell Biol. 1993 Apr;13(4):2564–2577. doi: 10.1128/mcb.13.4.2564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Quantin B., Breathnach R. Epidermal growth factor stimulates transcription of the c-jun proto-oncogene in rat fibroblasts. Nature. 1988 Aug 11;334(6182):538–539. doi: 10.1038/334538a0. [DOI] [PubMed] [Google Scholar]
  28. Rozek D., Pfeifer G. P. In vivo protein-DNA interactions at the c-jun promoter: preformed complexes mediate the UV response. Mol Cell Biol. 1993 Sep;13(9):5490–5499. doi: 10.1128/mcb.13.9.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ryder K., Nathans D. Induction of protooncogene c-jun by serum growth factors. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8464–8467. doi: 10.1073/pnas.85.22.8464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tanaka M., Herr W. Differential transcriptional activation by Oct-1 and Oct-2: interdependent activation domains induce Oct-2 phosphorylation. Cell. 1990 Feb 9;60(3):375–386. doi: 10.1016/0092-8674(90)90589-7. [DOI] [PubMed] [Google Scholar]
  31. Tanaka M., Lai J. S., Herr W. Promoter-selective activation domains in Oct-1 and Oct-2 direct differential activation of an snRNA and mRNA promoter. Cell. 1992 Feb 21;68(4):755–767. doi: 10.1016/0092-8674(92)90150-b. [DOI] [PubMed] [Google Scholar]
  32. Treisman R. Ternary complex factors: growth factor regulated transcriptional activators. Curr Opin Genet Dev. 1994 Feb;4(1):96–101. doi: 10.1016/0959-437x(94)90097-3. [DOI] [PubMed] [Google Scholar]
  33. Treisman R. The SRE: a growth factor responsive transcriptional regulator. Semin Cancer Biol. 1990 Feb;1(1):47–58. [PubMed] [Google Scholar]
  34. Treisman R. The serum response element. Trends Biochem Sci. 1992 Oct;17(10):423–426. doi: 10.1016/0968-0004(92)90013-y. [DOI] [PubMed] [Google Scholar]
  35. Wentworth B. M., Donoghue M., Engert J. C., Berglund E. B., Rosenthal N. Paired MyoD-binding sites regulate myosin light chain gene expression. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1242–1246. doi: 10.1073/pnas.88.4.1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yee S. P., Rigby P. W. The regulation of myogenin gene expression during the embryonic development of the mouse. Genes Dev. 1993 Jul;7(7A):1277–1289. doi: 10.1101/gad.7.7a.1277. [DOI] [PubMed] [Google Scholar]
  37. Yu Y. T., Breitbart R. E., Smoot L. B., Lee Y., Mahdavi V., Nadal-Ginard B. Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors. Genes Dev. 1992 Sep;6(9):1783–1798. doi: 10.1101/gad.6.9.1783. [DOI] [PubMed] [Google Scholar]
  38. Zhu H., Garcia A. V., Ross R. S., Evans S. M., Chien K. R. A conserved 28-base-pair element (HF-1) in the rat cardiac myosin light-chain-2 gene confers cardiac-specific and alpha-adrenergic-inducible expression in cultured neonatal rat myocardial cells. Mol Cell Biol. 1991 Apr;11(4):2273–2281. doi: 10.1128/mcb.11.4.2273. [DOI] [PMC free article] [PubMed] [Google Scholar]

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