Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1994 Mar;14(3):1870–1885. doi: 10.1128/mcb.14.3.1870

A novel myogenic regulatory circuit controls slow/cardiac troponin C gene transcription in skeletal muscle.

M S Parmacek 1, H S Ip 1, F Jung 1, T Shen 1, J F Martin 1, A J Vora 1, E N Olson 1, J M Leiden 1
PMCID: PMC358545  PMID: 8114720

Abstract

The slow/cardiac troponin C (cTnC) gene is expressed in three distinct striated muscle lineages: cardiac myocytes, embryonic fast skeletal myotubes, and adult slow skeletal myocytes. We have reported previously that cTnC gene expression in cardiac muscle is regulated by a cardiac-specific promoter/enhancer located in the 5' flanking region of the gene (bp -124 to +1). In this report, we demonstrate that the cTnC gene contains a second distinct and independent transcriptional enhancer which is located in the first intron. This second enhancer is skeletal myotube specific and is developmentally up-regulated during the differentiation of myoblasts to myotubes. This enhancer contains three functionally important nuclear protein binding sites: a CACCC box, a MEF-2 binding site, and a previously undescribed nuclear protein binding site, designated MEF-3, which is also present in a large number of skeletal muscle-specific transcriptional enhancers. Unlike most skeletal muscle-specific transcriptional regulatory elements, the cTnC enhancer does not contain a consensus binding site (CANNTG) for the basic helix-loop-helix (bHLH) family of transcription factors and does not directly bind MyoD-E12 protein complexes. Despite these findings, the cTnC enhancer can be transactivated by overexpression of the myogenic bHLH proteins, MyoD and myogenin, in C3H10T1/2 (10T1/2) cells. Electrophoretic mobility shift assays demonstrated changes in the patterns of MEF-2, CACCC, and MEF-3 DNA binding activities following the conversion of 10T1/2 cells into myoblasts and myotubes by stable transfection with a MyoD expression vector. In particular, MEF-2 binding activity was up-regulated in 10T1/2 cells stably transfected with a MyoD expression vector only after these cells fused and differentiated into skeletal myotubes. Taken together, these results demonstrated that distinct lineage-specific transcriptional regulatory elements control the expression of a single myofibrillar protein gene in fast skeletal and cardiac muscle. In addition, they show that bHLH transcription factors can indirectly transactivate the expression of some muscle-specific genes.

Full text

PDF
1870

Images in this article

Selected References

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

  1. Braun T., Bober E., Winter B., Rosenthal N., Arnold H. H. Myf-6, a new member of the human gene family of myogenic determination factors: evidence for a gene cluster on chromosome 12. EMBO J. 1990 Mar;9(3):821–831. doi: 10.1002/j.1460-2075.1990.tb08179.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Braun T., Buschhausen-Denker G., Bober E., Tannich E., Arnold H. H. A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts. EMBO J. 1989 Mar;8(3):701–709. doi: 10.1002/j.1460-2075.1989.tb03429.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Braun T., Rudnicki M. A., Arnold H. H., Jaenisch R. Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death. Cell. 1992 Oct 30;71(3):369–382. doi: 10.1016/0092-8674(92)90507-9. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Brennan T. J., Chakraborty T., Olson E. N. Mutagenesis of the myogenin basic region identifies an ancient protein motif critical for activation of myogenesis. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5675–5679. doi: 10.1073/pnas.88.13.5675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brennan T. J., Olson E. N. Myogenin resides in the nucleus and acquires high affinity for a conserved enhancer element on heterodimerization. Genes Dev. 1990 Apr;4(4):582–595. doi: 10.1101/gad.4.4.582. [DOI] [PubMed] [Google Scholar]
  7. Bucher E. A., Maisonpierre P. C., Konieczny S. F., Emerson C. P., Jr Expression of the troponin complex genes: transcriptional coactivation during myoblast differentiation and independent control in heart and skeletal muscles. Mol Cell Biol. 1988 Oct;8(10):4134–4142. doi: 10.1128/mcb.8.10.4134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Davis R. L., Weintraub H. Acquisition of myogenic specificity by replacement of three amino acid residues from MyoD into E12. Science. 1992 May 15;256(5059):1027–1030. doi: 10.1126/science.1317057. [DOI] [PubMed] [Google Scholar]
  10. Davis R. L., Weintraub H., Lassar A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987 Dec 24;51(6):987–1000. doi: 10.1016/0092-8674(87)90585-x. [DOI] [PubMed] [Google Scholar]
  11. Devlin B. H., Wefald F. C., Kraus W. E., Bernard T. S., Williams R. S. Identification of a muscle-specific enhancer within the 5'-flanking region of the human myoglobin gene. J Biol Chem. 1989 Aug 15;264(23):13896–13901. [PubMed] [Google Scholar]
  12. Dhoot G. K., Perry S. V. Distribution of polymorphic forms of troponin components and tropomyosin in skeletal muscle. Nature. 1979 Apr 19;278(5706):714–718. doi: 10.1038/278714a0. [DOI] [PubMed] [Google Scholar]
  13. Dierks P., van Ooyen A., Cochran M. D., Dobkin C., Reiser J., Weissmann C. Three regions upstream from the cap site are required for efficient and accurate transcription of the rabbit beta-globin gene in mouse 3T6 cells. Cell. 1983 Mar;32(3):695–706. doi: 10.1016/0092-8674(83)90055-7. [DOI] [PubMed] [Google Scholar]
  14. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Donoghue M., Ernst H., Wentworth B., Nadal-Ginard B., Rosenthal N. A muscle-specific enhancer is located at the 3' end of the myosin light-chain 1/3 gene locus. Genes Dev. 1988 Dec;2(12B):1779–1790. doi: 10.1101/gad.2.12b.1779. [DOI] [PubMed] [Google Scholar]
  16. Edmondson D. G., Cheng T. C., Cserjesi P., Chakraborty T., Olson E. N. Analysis of the myogenin promoter reveals an indirect pathway for positive autoregulation mediated by the muscle-specific enhancer factor MEF-2. Mol Cell Biol. 1992 Sep;12(9):3665–3677. doi: 10.1128/mcb.12.9.3665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Edmondson D. G., Olson E. N. A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program. Genes Dev. 1989 May;3(5):628–640. doi: 10.1101/gad.3.5.628. [DOI] [PubMed] [Google Scholar]
  18. Frampton J., Walker M., Plumb M., Harrison P. R. Synergy between the NF-E1 erythroid-specific transcription factor and the CACCC factor in the erythroid-specific promoter of the human porphobilinogen deaminase gene. Mol Cell Biol. 1990 Jul;10(7):3838–3842. doi: 10.1128/mcb.10.7.3838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. French B. A., Chow K. L., Olson E. N., Schwartz R. J. Heterodimers of myogenic helix-loop-helix regulatory factors and E12 bind a complex element governing myogenic induction of the avian cardiac alpha-actin promoter. Mol Cell Biol. 1991 May;11(5):2439–2450. doi: 10.1128/mcb.11.5.2439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gahlmann R., Kedes L. Cloning, structural analysis, and expression of the human fast twitch skeletal muscle troponin C gene. J Biol Chem. 1990 Jul 25;265(21):12520–12528. [PubMed] [Google Scholar]
  21. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gorman C., Padmanabhan R., Howard B. H. High efficiency DNA-mediated transformation of primate cells. Science. 1983 Aug 5;221(4610):551–553. doi: 10.1126/science.6306768. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Gottschalk L. R., Leiden J. M. Identification and functional characterization of the human T-cell receptor beta gene transcriptional enhancer: common nuclear proteins interact with the transcriptional regulatory elements of the T-cell receptor alpha and beta genes. Mol Cell Biol. 1990 Oct;10(10):5486–5495. doi: 10.1128/mcb.10.10.5486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Gustafson T. A., Miwa T., Boxer L. M., Kedes L. Interaction of nuclear proteins with muscle-specific regulatory sequences of the human cardiac alpha-actin promoter. Mol Cell Biol. 1988 Oct;8(10):4110–4119. doi: 10.1128/mcb.8.10.4110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hasty P., Bradley A., Morris J. H., Edmondson D. G., Venuti J. M., Olson E. N., Klein W. H. Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene. Nature. 1993 Aug 5;364(6437):501–506. doi: 10.1038/364501a0. [DOI] [PubMed] [Google Scholar]
  27. Henderson S. A., Spencer M., Sen A., Kumar C., Siddiqui M. A., Chien K. R. Structure, organization, and expression of the rat cardiac myosin light chain-2 gene. Identification of a 250-base pair fragment which confers cardiac-specific expression. J Biol Chem. 1989 Oct 25;264(30):18142–18148. [PubMed] [Google Scholar]
  28. Herzberg O., Moult J., James M. N. Molecular structure of troponin C and its implications for the Ca2+ triggering of muscle contraction. Methods Enzymol. 1987;139:610–632. doi: 10.1016/0076-6879(87)39115-3. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. Iannello R. C., Mar J. H., Ordahl C. P. Characterization of a promoter element required for transcription in myocardial cells. J Biol Chem. 1991 Feb 15;266(5):3309–3316. [PubMed] [Google Scholar]
  32. Jaynes J. B., Johnson J. E., Buskin J. N., Gartside C. L., Hauschka S. D. The muscle creatine kinase gene is regulated by multiple upstream elements, including a muscle-specific enhancer. Mol Cell Biol. 1988 Jan;8(1):62–70. doi: 10.1128/mcb.8.1.62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Johnson J. E., Wold B. J., Hauschka S. D. Muscle creatine kinase sequence elements regulating skeletal and cardiac muscle expression in transgenic mice. Mol Cell Biol. 1989 Aug;9(8):3393–3399. doi: 10.1128/mcb.9.8.3393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Karpinski B. A., Yang L. H., Cacheris P., Morle G. D., Leiden J. M. The first intron of the 4F2 heavy-chain gene contains a transcriptional enhancer element that binds multiple nuclear proteins. Mol Cell Biol. 1989 Jun;9(6):2588–2597. doi: 10.1128/mcb.9.6.2588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Klamut H. J., Gangopadhyay S. B., Worton R. G., Ray P. N. Molecular and functional analysis of the muscle-specific promoter region of the Duchenne muscular dystrophy gene. Mol Cell Biol. 1990 Jan;10(1):193–205. doi: 10.1128/mcb.10.1.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lassar A. B., Buskin J. N., Lockshon D., Davis R. L., Apone S., Hauschka S. D., Weintraub H. MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer. Cell. 1989 Sep 8;58(5):823–831. doi: 10.1016/0092-8674(89)90935-5. [DOI] [PubMed] [Google Scholar]
  37. Leavis P. C., Gergely J. Thin filament proteins and thin filament-linked regulation of vertebrate muscle contraction. CRC Crit Rev Biochem. 1984;16(3):235–305. doi: 10.3109/10409238409108717. [DOI] [PubMed] [Google Scholar]
  38. Lee H. R., Henderson S. A., Reynolds R., Dunnmon P., Yuan D., Chien K. R. Alpha 1-adrenergic stimulation of cardiac gene transcription in neonatal rat myocardial cells. Effects on myosin light chain-2 gene expression. J Biol Chem. 1988 May 25;263(15):7352–7358. [PubMed] [Google Scholar]
  39. Lee K. J., Ross R. S., Rockman H. A., Harris A. N., O'Brien T. X., van Bilsen M., Shubeita H. E., Kandolf R., Brem G., Price J. Myosin light chain-2 luciferase transgenic mice reveal distinct regulatory programs for cardiac and skeletal muscle-specific expression of a single contractile protein gene. J Biol Chem. 1992 Aug 5;267(22):15875–15885. [PubMed] [Google Scholar]
  40. Leung K., Nabel G. J. HTLV-1 transactivator induces interleukin-2 receptor expression through an NF-kappa B-like factor. Nature. 1988 Jun 23;333(6175):776–778. doi: 10.1038/333776a0. [DOI] [PubMed] [Google Scholar]
  41. Lin H., Parmacek M. S., Morle G., Bolling S., Leiden J. M. Expression of recombinant genes in myocardium in vivo after direct injection of DNA. Circulation. 1990 Dec;82(6):2217–2221. doi: 10.1161/01.cir.82.6.2217. [DOI] [PubMed] [Google Scholar]
  42. Lin H., Yutzey K. E., Konieczny S. F. Muscle-specific expression of the troponin I gene requires interactions between helix-loop-helix muscle regulatory factors and ubiquitous transcription factors. Mol Cell Biol. 1991 Jan;11(1):267–280. doi: 10.1128/mcb.11.1.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Mantovani R., Malgaretti N., Nicolis S., Giglioni B., Comi P., Cappellini N., Bertero M. T., Caligaris-Cappio F., Ottolenghi S. An erythroid specific nuclear factor binding to the proximal CACCC box of the beta-globin gene promoter. Nucleic Acids Res. 1988 May 25;16(10):4299–4313. doi: 10.1093/nar/16.10.4299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Mar J. H., Ordahl C. P. A conserved CATTCCT motif is required for skeletal muscle-specific activity of the cardiac troponin T gene promoter. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6404–6408. doi: 10.1073/pnas.85.17.6404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Mar J. H., Ordahl C. P. M-CAT binding factor, a novel trans-acting factor governing muscle-specific transcription. Mol Cell Biol. 1990 Aug;10(8):4271–4283. doi: 10.1128/mcb.10.8.4271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. 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]
  47. 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]
  48. 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]
  49. Miner J. H., Wold B. Herculin, a fourth member of the MyoD family of myogenic regulatory genes. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1089–1093. doi: 10.1073/pnas.87.3.1089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Murre C., McCaw P. S., Vaessin H., Caudy M., Jan L. Y., Jan Y. N., Cabrera C. V., Buskin J. N., Hauschka S. D., Lassar A. B. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989 Aug 11;58(3):537–544. doi: 10.1016/0092-8674(89)90434-0. [DOI] [PubMed] [Google Scholar]
  51. Olson E. N. MyoD family: a paradigm for development? Genes Dev. 1990 Sep;4(9):1454–1461. doi: 10.1101/gad.4.9.1454. [DOI] [PubMed] [Google Scholar]
  52. Parmacek M. S., Bengur A. R., Vora A. J., Leiden J. M. The structure and regulation of expression of the murine fast skeletal troponin C gene. Identification of a developmentally regulated, muscle-specific transcriptional enhancer. J Biol Chem. 1990 Sep 15;265(26):15970–15976. [PubMed] [Google Scholar]
  53. Parmacek M. S., Leiden J. M. Structure and expression of the murine slow/cardiac troponin C gene. J Biol Chem. 1989 Aug 5;264(22):13217–13225. [PubMed] [Google Scholar]
  54. Parmacek M. S., Leiden J. M. Structure, function, and regulation of troponin C. Circulation. 1991 Sep;84(3):991–1003. doi: 10.1161/01.cir.84.3.991. [DOI] [PubMed] [Google Scholar]
  55. Parmacek M. S., Vora A. J., Shen T., Barr E., Jung F., Leiden J. M. Identification and characterization of a cardiac-specific transcriptional regulatory element in the slow/cardiac troponin C gene. Mol Cell Biol. 1992 May;12(5):1967–1976. doi: 10.1128/mcb.12.5.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Piette J., Bessereau J. L., Huchet M., Changeux J. P. Two adjacent MyoD1-binding sites regulate expression of the acetylcholine receptor alpha-subunit gene. Nature. 1990 May 24;345(6273):353–355. doi: 10.1038/345353a0. [DOI] [PubMed] [Google Scholar]
  57. 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]
  58. Prost E., Moore D. D. CAT vectors for analysis of eukaryotic promoters and enhancers. Gene. 1986;45(1):107–111. doi: 10.1016/0378-1119(86)90138-1. [DOI] [PubMed] [Google Scholar]
  59. Rhodes S. J., Konieczny S. F. Identification of MRF4: a new member of the muscle regulatory factor gene family. Genes Dev. 1989 Dec;3(12B):2050–2061. doi: 10.1101/gad.3.12b.2050. [DOI] [PubMed] [Google Scholar]
  60. Rosenthal N., Berglund E. B., Wentworth B. M., Donoghue M., Winter B., Bober E., Braun T., Arnold H. H. A highly conserved enhancer downstream of the human MLC1/3 locus is a target for multiple myogenic determination factors. Nucleic Acids Res. 1990 Nov 11;18(21):6239–6246. doi: 10.1093/nar/18.21.6239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Rudnicki M. A., Braun T., Hinuma S., Jaenisch R. Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development. Cell. 1992 Oct 30;71(3):383–390. doi: 10.1016/0092-8674(92)90508-a. [DOI] [PubMed] [Google Scholar]
  62. Sartorelli V., Webster K. A., Kedes L. Muscle-specific expression of the cardiac alpha-actin gene requires MyoD1, CArG-box binding factor, and Sp1. Genes Dev. 1990 Oct;4(10):1811–1822. doi: 10.1101/gad.4.10.1811. [DOI] [PubMed] [Google Scholar]
  63. Sassoon D. A., Garner I., Buckingham M. Transcripts of alpha-cardiac and alpha-skeletal actins are early markers for myogenesis in the mouse embryo. Development. 1988 Sep;104(1):155–164. doi: 10.1242/dev.104.1.155. [DOI] [PubMed] [Google Scholar]
  64. Schreier T., Kedes L., Gahlmann R. Cloning, structural analysis, and expression of the human slow twitch skeletal muscle/cardiac troponin C gene. J Biol Chem. 1990 Dec 5;265(34):21247–21253. [PubMed] [Google Scholar]
  65. Schüle R., Muller M., Otsuka-Murakami H., Renkawitz R. Cooperativity of the glucocorticoid receptor and the CACCC-box binding factor. Nature. 1988 Mar 3;332(6159):87–90. doi: 10.1038/332087a0. [DOI] [PubMed] [Google Scholar]
  66. Seidel U., Arnold H. H. Identification of the functional promoter regions in the human gene encoding the myosin alkali light chains MLC1 and MLC3 of fast skeletal muscle. J Biol Chem. 1989 Sep 25;264(27):16109–16117. [PubMed] [Google Scholar]
  67. Shen R. A., Goswami S. K., Mascareno E., Kumar A., Siddiqui M. A. Tissue-specific transcription of the cardiac myosin light-chain 2 gene is regulated by an upstream repressor element. Mol Cell Biol. 1991 Mar;11(3):1676–1685. doi: 10.1128/mcb.11.3.1676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Sternberg E. A., Spizz G., Perry W. M., Vizard D., Weil T., Olson E. N. Identification of upstream and intragenic regulatory elements that confer cell-type-restricted and differentiation-specific expression on the muscle creatine kinase gene. Mol Cell Biol. 1988 Jul;8(7):2896–2909. doi: 10.1128/mcb.8.7.2896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Tapscott S. J., Weintraub H. MyoD and the regulation of myogenesis by helix-loop-helix proteins. J Clin Invest. 1991 Apr;87(4):1133–1138. doi: 10.1172/JCI115109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Trask R. V., Strauss A. W., Billadello J. J. Developmental regulation and tissue-specific expression of the human muscle creatine kinase gene. J Biol Chem. 1988 Nov 15;263(32):17142–17149. [PubMed] [Google Scholar]
  71. Voronova A., Baltimore D. Mutations that disrupt DNA binding and dimer formation in the E47 helix-loop-helix protein map to distinct domains. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4722–4726. doi: 10.1073/pnas.87.12.4722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Weintraub H., Davis R., Lockshon D., Lassar A. MyoD binds cooperatively to two sites in a target enhancer sequence: occupancy of two sites is required for activation. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5623–5627. doi: 10.1073/pnas.87.15.5623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Weintraub H., Davis R., Tapscott S., Thayer M., Krause M., Benezra R., Blackwell T. K., Turner D., Rupp R., Hollenberg S. The myoD gene family: nodal point during specification of the muscle cell lineage. Science. 1991 Feb 15;251(4995):761–766. doi: 10.1126/science.1846704. [DOI] [PubMed] [Google Scholar]
  74. Weintraub H., Tapscott S. J., Davis R. L., Thayer M. J., Adam M. A., Lassar A. B., Miller A. D. Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5434–5438. doi: 10.1073/pnas.86.14.5434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. 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]
  76. Wilkinson J. M. Troponin C from rabbit slow skeletal and cardiac muscle is the product of a single gene. Eur J Biochem. 1980 Jan;103(1):179–188. doi: 10.1111/j.1432-1033.1980.tb04302.x. [DOI] [PubMed] [Google Scholar]
  77. Wright W. E., Sassoon D. A., Lin V. K. Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD. Cell. 1989 Feb 24;56(4):607–617. doi: 10.1016/0092-8674(89)90583-7. [DOI] [PubMed] [Google Scholar]
  78. Xiao J. H., Davidson I., Matthes H., Garnier J. M., Chambon P. Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1. Cell. 1991 May 17;65(4):551–568. doi: 10.1016/0092-8674(91)90088-g. [DOI] [PubMed] [Google Scholar]
  79. 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]
  80. Yutzey K. E., Kline R. L., Konieczny S. F. An internal regulatory element controls troponin I gene expression. Mol Cell Biol. 1989 Apr;9(4):1397–1405. doi: 10.1128/mcb.9.4.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Zeller R., Bloch K. D., Williams B. S., Arceci R. J., Seidman C. E. Localized expression of the atrial natriuretic factor gene during cardiac embryogenesis. Genes Dev. 1987 Sep;1(7):693–698. doi: 10.1101/gad.1.7.693. [DOI] [PubMed] [Google Scholar]
  82. Zot A. S., Potter J. D., Strauss W. L. Isolation and sequence of a cDNA clone for rabbit fast skeletal muscle troponin C. Homology with calmodulin and parvalbumin. J Biol Chem. 1987 Nov 15;262(32):15418–15421. [PubMed] [Google Scholar]

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

RESOURCES