Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1997 Feb;17(2):656–666. doi: 10.1128/mcb.17.2.656

A combination of MEF3 and NFI proteins activates transcription in a subset of fast-twitch muscles.

F Spitz 1, M Salminen 1, J Demignon 1, A Kahn 1, D Daegelen 1, P Maire 1
PMCID: PMC231791  PMID: 9001219

Abstract

The human aldolase A pM promoter is active in fast-twitch muscles. To understand the role of the different transcription factors which bind to this promoter and determine which ones are responsible for its restricted pattern of expression, we analyzed several transgenic lines harboring different combinations of pM regulatory elements. We show that muscle-specific expression can be achieved without any binding sites for the myogenic factors MyoD and MEF2 and that a 64-bp fragment comprising a MEF3 motif and an NFI binding site is sufficient to drive reporter gene expression in some but, interestingly, not all fast-twitch muscles. A result related to this pattern of expression is that some isoforms of NFI proteins accumulate differentially in fast- and slow-twitch muscles and in distinct fast-twitch muscles. We propose that these isoforms of NFI proteins might provide a molecular basis for skeletal muscle diversity.

Full Text

The Full Text of this article is available as a PDF (364.5 KB).

Selected References

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

  1. Allen N. D., Cran D. G., Barton S. C., Hettle S., Reik W., Surani M. A. Transgenes as probes for active chromosomal domains in mouse development. Nature. 1988 Jun 30;333(6176):852–855. doi: 10.1038/333852a0. [DOI] [PubMed] [Google Scholar]
  2. Apt D., Liu Y., Bernard H. U. Cloning and functional analysis of spliced isoforms of human nuclear factor I-X: interference with transcriptional activation by NFI/CTF in a cell-type specific manner. Nucleic Acids Res. 1994 Sep 25;22(19):3825–3833. doi: 10.1093/nar/22.19.3825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Banerjee-Basu S., Buonanno A. cis-acting sequences of the rat troponin I slow gene confer tissue- and development-specific transcription in cultured muscle cells as well as fiber type specificity in transgenic mice. Mol Cell Biol. 1993 Nov;13(11):7019–7028. doi: 10.1128/mcb.13.11.7019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baylies M. K., Martinez Arias A., Bate M. wingless is required for the formation of a subset of muscle founder cells during Drosophila embryogenesis. Development. 1995 Nov;121(11):3829–3837. doi: 10.1242/dev.121.11.3829. [DOI] [PubMed] [Google Scholar]
  5. Buckingham M. E. Muscle: the regulation of myogenesis. Curr Opin Genet Dev. 1994 Oct;4(5):745–751. doi: 10.1016/0959-437x(94)90142-p. [DOI] [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. Concordet J. P., Salminen M., Demignon J., Moch C., Maire P., Kahn A., Daegelen D. An opportunistic promoter sharing regulatory sequences with either a muscle-specific or a ubiquitous promoter in the human aldolase A gene. Mol Cell Biol. 1993 Jan;13(1):9–17. doi: 10.1128/mcb.13.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Corin S. J., Levitt L. K., O'Mahoney J. V., Joya J. E., Hardeman E. C., Wade R. Delineation of a slow-twitch-myofiber-specific transcriptional element by using in vivo somatic gene transfer. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6185–6189. doi: 10.1073/pnas.92.13.6185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DiMario J. X., Fernyak S. E., Stockdale F. E. Myoblasts transferred to the limbs of embryos are committed to specific fibre fates. Nature. 1993 Mar 11;362(6416):165–167. doi: 10.1038/362165a0. [DOI] [PubMed] [Google Scholar]
  10. Donoghue M. J., Alvarez J. D., Merlie J. P., Sanes J. R. Fiber type- and position-dependent expression of a myosin light chain-CAT transgene detected with a novel histochemical stain for CAT. J Cell Biol. 1991 Oct;115(2):423–434. doi: 10.1083/jcb.115.2.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Donoghue M. J., Sanes J. R. All muscles are not created equal. Trends Genet. 1994 Nov;10(11):396–401. doi: 10.1016/0168-9525(94)90056-6. [DOI] [PubMed] [Google Scholar]
  12. Donoviel D. B., Shield M. A., Buskin J. N., Haugen H. S., Clegg C. H., Hauschka S. D. Analysis of muscle creatine kinase gene regulatory elements in skeletal and cardiac muscles of transgenic mice. Mol Cell Biol. 1996 Apr;16(4):1649–1658. doi: 10.1128/mcb.16.4.1649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Funk W. D., Wright W. E. Cyclic amplification and selection of targets for multicomponent complexes: myogenin interacts with factors recognizing binding sites for basic helix-loop-helix, nuclear factor 1, myocyte-specific enhancer-binding factor 2, and COMP1 factor. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9484–9488. doi: 10.1073/pnas.89.20.9484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gorski K., Carneiro M., Schibler U. Tissue-specific in vitro transcription from the mouse albumin promoter. Cell. 1986 Dec 5;47(5):767–776. doi: 10.1016/0092-8674(86)90519-2. [DOI] [PubMed] [Google Scholar]
  15. Hallauer P. L., Bradshaw H. L., Hastings K. E. Complex fiber-type-specific expression of fast skeletal muscle troponin I gene constructs in transgenic mice. Development. 1993 Nov;119(3):691–701. doi: 10.1242/dev.119.3.691. [DOI] [PubMed] [Google Scholar]
  16. Hatta K., Schilling T. F., BreMiller R. A., Kimmel C. B. Specification of jaw muscle identity in zebrafish: correlation with engrailed-homeoprotein expression. Science. 1990 Nov 9;250(4982):802–805. doi: 10.1126/science.1978412. [DOI] [PubMed] [Google Scholar]
  17. Hidaka K., Yamamoto I., Arai Y., Mukai T. The MEF-3 motif is required for MEF-2-mediated skeletal muscle-specific induction of the rat aldolase A gene. Mol Cell Biol. 1993 Oct;13(10):6469–6478. doi: 10.1128/mcb.13.10.6469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hämäläinen N., Pette D. The histochemical profiles of fast fiber types IIB, IID, and IIA in skeletal muscles of mouse, rat, and rabbit. J Histochem Cytochem. 1993 May;41(5):733–743. doi: 10.1177/41.5.8468455. [DOI] [PubMed] [Google Scholar]
  19. Izumo S., Nadal-Ginard B., Mahdavi V. All members of the MHC multigene family respond to thyroid hormone in a highly tissue-specific manner. Science. 1986 Feb 7;231(4738):597–600. doi: 10.1126/science.3945800. [DOI] [PubMed] [Google Scholar]
  20. Jackson S. P., Tjian R. Purification and analysis of RNA polymerase II transcription factors by using wheat germ agglutinin affinity chromatography. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1781–1785. doi: 10.1073/pnas.86.6.1781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Joh K., Mukai T., Motomura M., Oh-uchida M., Yatsuki H., Hori K. Expression of rat aldolase A gene and analysis of AH promoter region of the gene. Prog Clin Biol Res. 1990;344:53–73. [PubMed] [Google Scholar]
  22. Kelly R., Alonso S., Tajbakhsh S., Cossu G., Buckingham M. Myosin light chain 3F regulatory sequences confer regionalized cardiac and skeletal muscle expression in transgenic mice. J Cell Biol. 1995 Apr;129(2):383–396. doi: 10.1083/jcb.129.2.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Knotts S., Rindt H., Neumann J., Robbins J. In vivo regulation of the mouse beta myosin heavy chain gene. J Biol Chem. 1994 Dec 9;269(49):31275–31282. [PubMed] [Google Scholar]
  24. Koffer A., Brownson C. Fractionation of nuclear proteins from red and white skeletal muscle, heart and liver of rabbit. Int J Biochem. 1979;10(10):845–857. doi: 10.1016/0020-711x(79)90058-2. [DOI] [PubMed] [Google Scholar]
  25. Kruse U., Sippel A. E. The genes for transcription factor nuclear factor I give rise to corresponding splice variants between vertebrate species. J Mol Biol. 1994 May 20;238(5):860–865. doi: 10.1006/jmbi.1994.1343. [DOI] [PubMed] [Google Scholar]
  26. Kruse U., Sippel A. E. Transcription factor nuclear factor I proteins form stable homo- and heterodimers. FEBS Lett. 1994 Jul 4;348(1):46–50. doi: 10.1016/0014-5793(94)00585-0. [DOI] [PubMed] [Google Scholar]
  27. Laoide B. M., Foulkes N. S., Schlotter F., Sassone-Corsi P. The functional versatility of CREM is determined by its modular structure. EMBO J. 1993 Mar;12(3):1179–1191. doi: 10.1002/j.1460-2075.1993.tb05759.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lemaire P., Vesque C., Schmitt J., Stunnenberg H., Frank R., Charnay P. The serum-inducible mouse gene Krox-24 encodes a sequence-specific transcriptional activator. Mol Cell Biol. 1990 Jul;10(7):3456–3467. doi: 10.1128/mcb.10.7.3456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Maire P., Wuarin J., Schibler U. The role of cis-acting promoter elements in tissue-specific albumin gene expression. Science. 1989 Apr 21;244(4902):343–346. doi: 10.1126/science.2711183. [DOI] [PubMed] [Google Scholar]
  31. Merlie J. P., Mudd J., Cheng T. C., Olson E. N. Myogenin and acetylcholine receptor alpha gene promoters mediate transcriptional regulation in response to motor innervation. J Biol Chem. 1994 Jan 28;269(4):2461–2467. [PubMed] [Google Scholar]
  32. Moch C., Kahn A., Daegelen D. Independence and interdependence of the three human aldolase A promoters in transgenic mice. Gene Expr. 1996;6(1):1–14. [PMC free article] [PubMed] [Google Scholar]
  33. Molkentin J. D., Black B. L., Martin J. F., Olson E. N. Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins. Cell. 1995 Dec 29;83(7):1125–1136. doi: 10.1016/0092-8674(95)90139-6. [DOI] [PubMed] [Google Scholar]
  34. Nakayama M., Stauffer J., Cheng J., Banerjee-Basu S., Wawrousek E., Buonanno A. Common core sequences are found in skeletal muscle slow- and fast-fiber-type-specific regulatory elements. Mol Cell Biol. 1996 May;16(5):2408–2417. doi: 10.1128/mcb.16.5.2408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Nebl G., Cato A. C. NFI/X proteins: a class of NFI family of transcription factors with positive and negative regulatory domains. Cell Mol Biol Res. 1995;41(2):85–95. [PubMed] [Google Scholar]
  36. Parmacek M. S., Ip H. S., Jung F., Shen T., Martin J. F., Vora A. J., Olson E. N., Leiden J. M. A novel myogenic regulatory circuit controls slow/cardiac troponin C gene transcription in skeletal muscle. Mol Cell Biol. 1994 Mar;14(3):1870–1885. doi: 10.1128/mcb.14.3.1870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Patapoutian A., Miner J. H., Lyons G. E., Wold B. Isolated sequences from the linked Myf-5 and MRF4 genes drive distinct patterns of muscle-specific expression in transgenic mice. Development. 1993 May;118(1):61–69. doi: 10.1242/dev.118.1.61. [DOI] [PubMed] [Google Scholar]
  38. Pette D., Staron R. S. Cellular and molecular diversities of mammalian skeletal muscle fibers. Rev Physiol Biochem Pharmacol. 1990;116:1–76. doi: 10.1007/3540528806_3. [DOI] [PubMed] [Google Scholar]
  39. Puzianowska-Kuznicka M., Shi Y. B. Nuclear factor I as a potential regulator during postembryonic organ development. J Biol Chem. 1996 Mar 15;271(11):6273–6282. doi: 10.1074/jbc.271.11.6273. [DOI] [PubMed] [Google Scholar]
  40. Rao M. V., Donoghue M. J., Merlie J. P., Sanes J. R. Distinct regulatory elements control muscle-specific, fiber-type-selective, and axially graded expression of a myosin light-chain gene in transgenic mice. Mol Cell Biol. 1996 Jul;16(7):3909–3922. doi: 10.1128/mcb.16.7.3909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Raught B., Liao W. S., Rosen J. M. Developmentally and hormonally regulated CCAAT/enhancer-binding protein isoforms influence beta-casein gene expression. Mol Endocrinol. 1995 Sep;9(9):1223–1232. doi: 10.1210/mend.9.9.7491114. [DOI] [PubMed] [Google Scholar]
  42. Raymondjean M., Cereghini S., Yaniv M. Several distinct "CCAAT" box binding proteins coexist in eukaryotic cells. Proc Natl Acad Sci U S A. 1988 Feb;85(3):757–761. doi: 10.1073/pnas.85.3.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Roberts C. W., Sonder A. M., Lumsden A., Korsmeyer S. J. Development expression of Hox11 and specification of splenic cell fate. Am J Pathol. 1995 May;146(5):1089–1101. [PMC free article] [PubMed] [Google Scholar]
  44. Rosenthal N., Kornhauser J. M., Donoghue M., Rosen K. M., Merlie J. P. Myosin light chain enhancer activates muscle-specific, developmentally regulated gene expression in transgenic mice. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7780–7784. doi: 10.1073/pnas.86.20.7780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Roulet E., Armentero M. T., Krey G., Corthésy B., Dreyer C., Mermod N., Wahli W. Regulation of the DNA-binding and transcriptional activities of Xenopus laevis NFI-X by a novel C-terminal domain. Mol Cell Biol. 1995 Oct;15(10):5552–5562. doi: 10.1128/mcb.15.10.5552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Rupp R. A., Kruse U., Multhaup G., Göbel U., Beyreuther K., Sippel A. E. Chicken NFI/TGGCA proteins are encoded by at least three independent genes: NFI-A, NFI-B and NFI-C with homologues in mammalian genomes. Nucleic Acids Res. 1990 May 11;18(9):2607–2616. doi: 10.1093/nar/18.9.2607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Salminen M., López S., Maire P., Kahn A., Daegelen D. Fast-muscle-specific DNA-protein interactions occurring in vivo at the human aldolase A M promoter are necessary for correct promoter activity in transgenic mice. Mol Cell Biol. 1996 Jan;16(1):76–85. doi: 10.1128/mcb.16.1.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Salminen M., Maire P., Concordet J. P., Moch C., Porteu A., Kahn A., Daegelen D. Fast-muscle-specific expression of human aldolase A transgenes. Mol Cell Biol. 1994 Oct;14(10):6797–6808. doi: 10.1128/mcb.14.10.6797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Salminen M., Spitz F., Fiszman M. Y., Demignon J., Kahn A., Daegelen D., Maire P. Myotube-specific activity of the human aldolase A M-promoter requires an overlapping binding site for NF1 and MEF2 factors in addition to a binding site (M1) for unknown proteins. J Mol Biol. 1995 Oct 13;253(1):17–31. doi: 10.1006/jmbi.1995.0532. [DOI] [PubMed] [Google Scholar]
  50. Sanes J. R., Johnson Y. R., Kotzbauer P. T., Mudd J., Hanley T., Martinou J. C., Merlie J. P. Selective expression of an acetylcholine receptor-lacZ transgene in synaptic nuclei of adult muscle fibers. Development. 1991 Dec;113(4):1181–1191. doi: 10.1242/dev.113.4.1181. [DOI] [PubMed] [Google Scholar]
  51. Santoro C., Mermod N., Andrews P. C., Tjian R. A family of human CCAAT-box-binding proteins active in transcription and DNA replication: cloning and expression of multiple cDNAs. Nature. 1988 Jul 21;334(6179):218–224. doi: 10.1038/334218a0. [DOI] [PubMed] [Google Scholar]
  52. Stockdale F. E., Miller J. B. The cellular basis of myosin heavy chain isoform expression during development of avian skeletal muscles. Dev Biol. 1987 Sep;123(1):1–9. doi: 10.1016/0012-1606(87)90420-9. [DOI] [PubMed] [Google Scholar]
  53. Swillens S., Pirson I. Highly sensitive control of transcriptional activity by factor heterodimerization. Biochem J. 1994 Jul 1;301(Pt 1):9–12. doi: 10.1042/bj3010009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Wenzelides S., Altmann H., Wendler W., Winnacker E. L. CTF5--a new transcriptional activator of the NFI/CTF family. Nucleic Acids Res. 1996 Jun 15;24(12):2416–2421. doi: 10.1093/nar/24.12.2416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. de Wet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. doi: 10.1128/mcb.7.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES