Abstract
In transgenic mice, muscle-specific expression of the c-ski oncogene induces hypertrophy exclusively in a subset of fast muscle fibers. Here we report that regulatory elements from two genes expressed in fast fibers, myosin light chain 1/3 (MLC) and muscle creatine kinase (MCK), were activated when co-transfected with c-ski expression vectors in myoblasts. The expression from the MLC enhancer was reduced when the c-ski oncogene was cotransfected with MyoD into NIH3T3 fibroblasts. Activation of the MLC enhancer by Ski also occurred in vivo, since bigenic progeny generated by mating MLC-CAT and MSV-skitransgenic mice displayed higher CAT activity in their muscles than did the MLC-CAT parental line. Identification of gene targets for the fiber-specific action of the c-ski gene product provides a molecular model that could be used for the further dissection of Ski-induced hypertrophy, both in tissue culture and in vivo.
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- Barkas A. E., Brodeur D., Stavnezer E. Polyproteins containing a domain encoded by the V-SKI oncogene are located in the nuclei of SKV-transformed cells. Virology. 1986 May;151(1):131–138. doi: 10.1016/0042-6822(86)90111-x. [DOI] [PubMed] [Google Scholar]
- Blau H. M., Pavlath G. K., Hardeman E. C., Chiu C. P., Silberstein L., Webster S. G., Miller S. C., Webster C. Plasticity of the differentiated state. Science. 1985 Nov 15;230(4727):758–766. doi: 10.1126/science.2414846. [DOI] [PubMed] [Google Scholar]
- 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]
- Colmenares C., Stavnezer E. The ski oncogene induces muscle differentiation in quail embryo cells. Cell. 1989 Oct 20;59(2):293–303. doi: 10.1016/0092-8674(89)90291-2. [DOI] [PubMed] [Google Scholar]
- Colmenares C., Sutrave P., Hughes S. H., Stavnezer E. Activation of the c-ski oncogene by overexpression. J Virol. 1991 Sep;65(9):4929–4935. doi: 10.1128/jvi.65.9.4929-4935.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Colmenares C., Teumer J. K., Stavnezer E. Transformation-defective v-ski induces MyoD and myogenin expression but not myotube formation. Mol Cell Biol. 1991 Feb;11(2):1167–1170. doi: 10.1128/mcb.11.2.1167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- Ernst H., Walsh K., Harrison C. A., Rosenthal N. The myosin light chain enhancer and the skeletal actin promoter share a binding site for factors involved in muscle-specific gene expression. Mol Cell Biol. 1991 Jul;11(7):3735–3744. doi: 10.1128/mcb.11.7.3735. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Grieshammer U., Sassoon D., Rosenthal N. A transgene target for positional regulators marks early rostrocaudal specification of myogenic lineages. Cell. 1992 Apr 3;69(1):79–93. doi: 10.1016/0092-8674(92)90120-2. [DOI] [PubMed] [Google Scholar]
- Hinterberger T. J., Sassoon D. A., Rhodes S. J., Konieczny S. F. Expression of the muscle regulatory factor MRF4 during somite and skeletal myofiber development. Dev Biol. 1991 Sep;147(1):144–156. doi: 10.1016/s0012-1606(05)80014-4. [DOI] [PubMed] [Google Scholar]
- Hughes S. M., Blau H. M. Muscle fiber pattern is independent of cell lineage in postnatal rodent development. Cell. 1992 Feb 21;68(4):659–671. doi: 10.1016/0092-8674(92)90142-y. [DOI] [PubMed] [Google Scholar]
- Hughes S. M., Taylor J. M., Tapscott S. J., Gurley C. M., Carter W. J., Peterson C. A. Selective accumulation of MyoD and myogenin mRNAs in fast and slow adult skeletal muscle is controlled by innervation and hormones. Development. 1993 Aug;118(4):1137–1147. doi: 10.1242/dev.118.4.1137. [DOI] [PubMed] [Google Scholar]
- 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]
- Leferovich J. M., Lana D. P., Sutrave P., Hughes S. H., Kelly A. M. Regulation of c-ski transgene expression in developing and mature mice. J Neurosci. 1995 Jan;15(1 Pt 2):596–603. doi: 10.1523/JNEUROSCI.15-01-00596.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li Y., Turck C. M., Teumer J. K., Stavnezer E. Unique sequence, ski, in Sloan-Kettering avian retroviruses with properties of a new cell-derived oncogene. J Virol. 1986 Mar;57(3):1065–1072. doi: 10.1128/jvi.57.3.1065-1072.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lowey S., Risby D. Light chains from fast and slow muscle myosins. Nature. 1971 Nov 12;234(5324):81–85. doi: 10.1038/234081a0. [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]
- Nabeshima Y., Fujii-Kuriyama Y., Muramatsu M., Ogata K. Alternative transcription and two modes of splicing results in two myosin light chains from one gene. Nature. 1984 Mar 22;308(5957):333–338. doi: 10.1038/308333a0. [DOI] [PubMed] [Google Scholar]
- Nagase T., Mizuguchi G., Nomura N., Ishizaki R., Ueno Y., Ishii S. Requirement of protein co-factor for the DNA-binding function of the human ski proto-oncogene product. Nucleic Acids Res. 1990 Jan 25;18(2):337–343. doi: 10.1093/nar/18.2.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ott M. O., Bober E., Lyons G., Arnold H., Buckingham M. Early expression of the myogenic regulatory gene, myf-5, in precursor cells of skeletal muscle in the mouse embryo. Development. 1991 Apr;111(4):1097–1107. doi: 10.1242/dev.111.4.1097. [DOI] [PubMed] [Google Scholar]
- Robert B., Daubas P., Akimenko M. A., Cohen A., Garner I., Guenet J. L., Buckingham M. A single locus in the mouse encodes both myosin light chains 1 and 3, a second locus corresponds to a related pseudogene. Cell. 1984 Nov;39(1):129–140. doi: 10.1016/0092-8674(84)90198-3. [DOI] [PubMed] [Google Scholar]
- 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]
- Rosenthal N. Identification of regulatory elements of cloned genes with functional assays. Methods Enzymol. 1987;152:704–720. doi: 10.1016/0076-6879(87)52075-4. [DOI] [PubMed] [Google Scholar]
- 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]
- Sassoon D., Lyons G., Wright W. E., Lin V., Lassar A., Weintraub H., Buckingham M. Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis. Nature. 1989 Sep 28;341(6240):303–307. doi: 10.1038/341303a0. [DOI] [PubMed] [Google Scholar]
- Seed B., Sheen J. Y. A simple phase-extraction assay for chloramphenicol acyltransferase activity. Gene. 1988 Jul 30;67(2):271–277. doi: 10.1016/0378-1119(88)90403-9. [DOI] [PubMed] [Google Scholar]
- Stavnezer E., Brodeur D., Brennan L. A. The v-ski oncogene encodes a truncated set of c-ski coding exons with limited sequence and structural relatedness to v-myc. Mol Cell Biol. 1989 Sep;9(9):4038–4045. doi: 10.1128/mcb.9.9.4038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Stockdale F. E. Myogenic cell lineages. Dev Biol. 1992 Dec;154(2):284–298. doi: 10.1016/0012-1606(92)90068-r. [DOI] [PubMed] [Google Scholar]
- Sutrave P., Copeland T. D., Showalter S. D., Hughes S. H. Characterization of chicken c-ski oncogene products expressed by retrovirus vectors. Mol Cell Biol. 1990 Jun;10(6):3137–3144. doi: 10.1128/mcb.10.6.3137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sutrave P., Hughes S. H. Isolation and characterization of three distinct cDNAs for the chicken c-ski gene. Mol Cell Biol. 1989 Sep;9(9):4046–4051. doi: 10.1128/mcb.9.9.4046. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sutrave P., Kelly A. M., Hughes S. H. ski can cause selective growth of skeletal muscle in transgenic mice. Genes Dev. 1990 Sep;4(9):1462–1472. doi: 10.1101/gad.4.9.1462. [DOI] [PubMed] [Google Scholar]
- 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]
- Yaffe D., Saxel O. Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle. Nature. 1977 Dec 22;270(5639):725–727. doi: 10.1038/270725a0. [DOI] [PubMed] [Google Scholar]
- Yutzey K. E., Rhodes S. J., Konieczny S. F. Differential trans activation associated with the muscle regulatory factors MyoD1, myogenin, and MRF4. Mol Cell Biol. 1990 Aug;10(8):3934–3944. doi: 10.1128/mcb.10.8.3934. [DOI] [PMC free article] [PubMed] [Google Scholar]