Abstract
To identify the DNA sequences that regulate the expression of the sarcomeric myosin heavy-chain (MHC) genes in muscle cells, a series of deletion constructs of the rat embryonic MHC gene was assayed for transient expression after introduction into myogenic and nonmyogenic cells. The sequences in 1.4 kilobases of 5'-flanking DNA were found to be sufficient to direct expression of the MHC gene constructs in a tissue-specific manner (i.e., in differentiated muscle cells but not in undifferentiated muscle and nonmuscle cells). Three main distinct regulatory domains have been identified: (i) the upstream sequences from positions -1413 to -174, which determine the level of expression of the MHC gene and are constituted of three positive regulatory elements and two negative ones; (ii) a muscle-specific regulatory element from positions -173 to -142, which restricts the expression of the MHC gene to muscle cells; and (iii) the promoter region, downstream from position -102, which directs transcription initiation. Introduction of the simian virus 40 enhancer into constructs where subportions of or all of the upstream sequences are deleted (up to position -173) strongly increases the level of expression of such truncated constructs but without changing their muscle specificity. These upstream sequences, which can be substituted for by the simian virus 40 enhancer, function in an orientation-, position-, and promoter-dependent fashion. The muscle-specific element is also promoter specific but does not support efficient expression of the MHC gene. The MHC promoter in itself is not muscle specific. These results underline the importance of the concerted action of multiple regulatory elements that are likely to represent targets for DNA-binding-regulatory proteins.
Full text
PDF












Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andreadis A., Gallego M. E., Nadal-Ginard B. Generation of protein isoform diversity by alternative splicing: mechanistic and biological implications. Annu Rev Cell Biol. 1987;3:207–242. doi: 10.1146/annurev.cb.03.110187.001231. [DOI] [PubMed] [Google Scholar]
- Baldwin A. S., Jr, Kittler E. L., Emerson C. P., Jr Structure, evolution, and regulation of a fast skeletal muscle troponin I gene. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8080–8084. doi: 10.1073/pnas.82.23.8080. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Banerji J., Rusconi S., Schaffner W. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell. 1981 Dec;27(2 Pt 1):299–308. doi: 10.1016/0092-8674(81)90413-x. [DOI] [PubMed] [Google Scholar]
- Benoff S., Nadal-Ginard B. Transient induction of poly(A)-short myosin heavy chain messenger RNA during terminal differentiation of L6E9 myoblasts. J Mol Biol. 1980 Jun 25;140(2):283–298. doi: 10.1016/0022-2836(80)90106-0. [DOI] [PubMed] [Google Scholar]
- Berk A. J., Sharp P. A. Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids. Cell. 1977 Nov;12(3):721–732. doi: 10.1016/0092-8674(77)90272-0. [DOI] [PubMed] [Google Scholar]
- Blau H. M., Chiu C. P., Webster C. Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell. 1983 Apr;32(4):1171–1180. doi: 10.1016/0092-8674(83)90300-8. [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]
- Breitbart R. E., Andreadis A., Nadal-Ginard B. Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from single genes. Annu Rev Biochem. 1987;56:467–495. doi: 10.1146/annurev.bi.56.070187.002343. [DOI] [PubMed] [Google Scholar]
- Breitbart R. E., Nadal-Ginard B. Complete nucleotide sequence of the fast skeletal troponin T gene. Alternatively spliced exons exhibit unusual interspecies divergence. J Mol Biol. 1986 Apr 5;188(3):313–324. doi: 10.1016/0022-2836(86)90157-9. [DOI] [PubMed] [Google Scholar]
- Brutlag D. L., Clayton J., Friedland P., Kedes L. H. SEQ: a nucleotide sequence analysis and recombination system. Nucleic Acids Res. 1982 Jan 11;10(1):279–294. doi: 10.1093/nar/10.1.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buetti E., Kühnel B. Distinct sequence elements involved in the glucocorticoid regulation of the mouse mammary tumor virus promoter identified by linker scanning mutagenesis. J Mol Biol. 1986 Aug 5;190(3):379–389. doi: 10.1016/0022-2836(86)90009-4. [DOI] [PubMed] [Google Scholar]
- Butler-Browne G. S., Whalen R. G. Myosin isozyme transitions occurring during the postnatal development of the rat soleus muscle. Dev Biol. 1984 Apr;102(2):324–334. doi: 10.1016/0012-1606(84)90197-0. [DOI] [PubMed] [Google Scholar]
- Caplan A. I., Fiszman M. Y., Eppenberger H. M. Molecular and cell isoforms during development. Science. 1983 Sep 2;221(4614):921–927. doi: 10.1126/science.6348946. [DOI] [PubMed] [Google Scholar]
- Czosnek H., Nudel U., Shani M., Barker P. E., Pravtcheva D. D., Ruddle F. H., Yaffe D. The genes coding for the muscle contractile proteins, myosin heavy chain, myosin light chain 2, and skeletal muscle actin are located on three different mouse chromosomes. EMBO J. 1982;1(11):1299–1305. doi: 10.1002/j.1460-2075.1982.tb01314.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Derse D., Casey J. W. Two elements in the bovine leukemia virus long terminal repeat that regulate gene expression. Science. 1986 Mar 21;231(4744):1437–1440. doi: 10.1126/science.3006241. [DOI] [PubMed] [Google Scholar]
- Dynan W. S., Tjian R. Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. 1985 Aug 29-Sep 4Nature. 316(6031):774–778. doi: 10.1038/316774a0. [DOI] [PubMed] [Google Scholar]
- Edlund T., Walker M. D., Barr P. J., Rutter W. J. Cell-specific expression of the rat insulin gene: evidence for role of two distinct 5' flanking elements. Science. 1985 Nov 22;230(4728):912–916. doi: 10.1126/science.3904002. [DOI] [PubMed] [Google Scholar]
- Foster J., Stafford J., Queen C. An immunoglobulin promoter displays cell-type specificity independently of the enhancer. 1985 May 30-Jun 5Nature. 315(6018):423–425. doi: 10.1038/315423a0. [DOI] [PubMed] [Google Scholar]
- Godbout R., Ingram R., Tilghman S. M. Multiple regulatory elements in the intergenic region between the alpha-fetoprotein and albumin genes. Mol Cell Biol. 1986 Feb;6(2):477–487. doi: 10.1128/mcb.6.2.477. [DOI] [PMC free article] [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]
- 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]
- Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
- Grichnik J. M., Bergsma D. J., Schwartz R. J. Tissue restricted and stage specific transcription is maintained within 411 nucleotides flanking the 5' end of the chicken alpha-skeletal actin gene. Nucleic Acids Res. 1986 Feb 25;14(4):1683–1701. doi: 10.1093/nar/14.4.1683. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grosschedl R., Baltimore D. Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell. 1985 Jul;41(3):885–897. doi: 10.1016/s0092-8674(85)80069-6. [DOI] [PubMed] [Google Scholar]
- Gruss P., Dhar R., Khoury G. Simian virus 40 tandem repeated sequences as an element of the early promoter. Proc Natl Acad Sci U S A. 1981 Feb;78(2):943–947. doi: 10.1073/pnas.78.2.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gunning P., Ponte P., Blau H., Kedes L. alpha-skeletal and alpha-cardiac actin genes are coexpressed in adult human skeletal muscle and heart. Mol Cell Biol. 1983 Nov;3(11):1985–1995. doi: 10.1128/mcb.3.11.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haslinger A., Karin M. Upstream promoter element of the human metallothionein-IIA gene can act like an enhancer element. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8572–8576. doi: 10.1073/pnas.82.24.8572. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herr W., Clarke J. The SV40 enhancer is composed of multiple functional elements that can compensate for one another. Cell. 1986 May 9;45(3):461–470. doi: 10.1016/0092-8674(86)90332-6. [DOI] [PubMed] [Google Scholar]
- Imler J. L., Lemaire C., Wasylyk C., Wasylyk B. Negative regulation contributes to tissue specificity of the immunoglobulin heavy-chain enhancer. Mol Cell Biol. 1987 Jul;7(7):2558–2567. doi: 10.1128/mcb.7.7.2558. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Jaynes J. B., Chamberlain J. S., Buskin J. N., Johnson J. E., Hauschka S. D. Transcriptional regulation of the muscle creatine kinase gene and regulated expression in transfected mouse myoblasts. Mol Cell Biol. 1986 Aug;6(8):2855–2864. doi: 10.1128/mcb.6.8.2855. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Khoury G., Gruss P. Enhancer elements. Cell. 1983 Jun;33(2):313–314. doi: 10.1016/0092-8674(83)90410-5. [DOI] [PubMed] [Google Scholar]
- Kropp K., Gulick J., Robbins J. A canonical sequence organization at the 5'-end of the myosin heavy chain genes. J Biol Chem. 1986 May 15;261(14):6613–6618. [PubMed] [Google Scholar]
- Laimins L. A., Khoury G., Gorman C., Howard B., Gruss P. Host-specific activation of transcription by tandem repeats from simian virus 40 and Moloney murine sarcoma virus. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6453–6457. doi: 10.1073/pnas.79.21.6453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Learned R. M., Learned T. K., Haltiner M. M., Tjian R. T. Human rRNA transcription is modulated by the coordinate binding of two factors to an upstream control element. Cell. 1986 Jun 20;45(6):847–857. doi: 10.1016/0092-8674(86)90559-3. [DOI] [PubMed] [Google Scholar]
- Leinwand L. A., Fournier R. E., Nadal-Ginard B., Shows T. B. Multigene family for sarcomeric myosin heavy chain in mouse and human DNA: localization on a single chromosome. Science. 1983 Aug 19;221(4612):766–769. doi: 10.1126/science.6879174. [DOI] [PubMed] [Google Scholar]
- Lompré A. M., Nadal-Ginard B., Mahdavi V. Expression of the cardiac ventricular alpha- and beta-myosin heavy chain genes is developmentally and hormonally regulated. J Biol Chem. 1984 May 25;259(10):6437–6446. [PubMed] [Google Scholar]
- Maeda H., Kitamura D., Kudo A., Araki K., Watanabe T. Trans-acting nuclear protein responsible for induction of rearranged human immunoglobulin heavy chain gene. Cell. 1986 Apr 11;45(1):25–33. doi: 10.1016/0092-8674(86)90534-9. [DOI] [PubMed] [Google Scholar]
- Mahdavi V., Chambers A. P., Nadal-Ginard B. Cardiac alpha- and beta-myosin heavy chain genes are organized in tandem. Proc Natl Acad Sci U S A. 1984 May;81(9):2626–2630. doi: 10.1073/pnas.81.9.2626. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mason J. O., Williams G. T., Neuberger M. S. Transcription cell type specificity is conferred by an immunoglobulin VH gene promoter that includes a functional consensus sequence. Cell. 1985 Jun;41(2):479–487. doi: 10.1016/s0092-8674(85)80021-0. [DOI] [PubMed] [Google Scholar]
- Mayer Y., Czosnek H., Zeelon P. E., Yaffe D., Nudel U. Expression of the genes coding for the skeletal muscle and cardiac actions in the heart. Nucleic Acids Res. 1984 Jan 25;12(2):1087–1100. doi: 10.1093/nar/12.2.1087. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Medford R. M., Nguyen H. T., Nadal-Ginard B. Transcriptional and cell cycle-mediated regulation of myosin heavy chain gene expression during muscle cell differentiation. J Biol Chem. 1983 Sep 25;258(18):11063–11073. [PubMed] [Google Scholar]
- Melloul D., Aloni B., Calvo J., Yaffe D., Nudel U. Developmentally regulated expression of chimeric genes containing muscle actin DNA sequences in transfected myogenic cells. EMBO J. 1984 May;3(5):983–990. doi: 10.1002/j.1460-2075.1984.tb01917.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Messing J., Crea R., Seeburg P. H. A system for shotgun DNA sequencing. Nucleic Acids Res. 1981 Jan 24;9(2):309–321. doi: 10.1093/nar/9.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Minty A. J., Alonso S., Caravatti M., Buckingham M. E. A fetal skeletal muscle actin mRNA in the mouse and its identity with cardiac actin mRNA. Cell. 1982 Aug;30(1):185–192. doi: 10.1016/0092-8674(82)90024-1. [DOI] [PubMed] [Google Scholar]
- Minty A., Kedes L. Upstream regions of the human cardiac actin gene that modulate its transcription in muscle cells: presence of an evolutionarily conserved repeated motif. Mol Cell Biol. 1986 Jun;6(6):2125–2136. doi: 10.1128/mcb.6.6.2125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muglia L., Rothman-Denes L. B. Cell type-specific negative regulatory element in the control region of the rat alpha-fetoprotein gene. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7653–7657. doi: 10.1073/pnas.83.20.7653. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nadal-Ginard B. Commitment, fusion and biochemical differentiation of a myogenic cell line in the absence of DNA synthesis. Cell. 1978 Nov;15(3):855–864. doi: 10.1016/0092-8674(78)90270-2. [DOI] [PubMed] [Google Scholar]
- Nguyen H. T., Gubits R. M., Wydro R. M., Nadal-Ginard B. Sarcomeric myosin heavy chain is coded by a highly conserved multigene family. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5230–5234. doi: 10.1073/pnas.79.17.5230. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nir U., Walker M. D., Rutter W. J. Regulation of rat insulin 1 gene expression: evidence for negative regulation in nonpancreatic cells. Proc Natl Acad Sci U S A. 1986 May;83(10):3180–3184. doi: 10.1073/pnas.83.10.3180. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nudel U., Calvo J. M., Shani M., Levy Z. The nucleotide sequence of a rat myosin light chain 2 gene. Nucleic Acids Res. 1984 Sep 25;12(18):7175–7186. doi: 10.1093/nar/12.18.7175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohlsson H., Edlund T. Sequence-specific interactions of nuclear factors with the insulin gene enhancer. Cell. 1986 Apr 11;45(1):35–44. doi: 10.1016/0092-8674(86)90535-0. [DOI] [PubMed] [Google Scholar]
- Ott M. O., Sperling L., Herbomel P., Yaniv M., Weiss M. C. Tissue-specific expression is conferred by a sequence from the 5' end of the rat albumin gene. EMBO J. 1984 Nov;3(11):2505–2510. doi: 10.1002/j.1460-2075.1984.tb02164.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Periasamy M., Wydro R. M., Strehler-Page M. A., Strehler E. E., Nadal-Ginard B. Characterization of cDNA and genomic sequences corresponding to an embryonic myosin heavy chain. J Biol Chem. 1985 Dec 15;260(29):15856–15862. [PubMed] [Google Scholar]
- Rhodes D., Klug A. An underlying repeat in some transcriptional control sequences corresponding to half a double helical turn of DNA. Cell. 1986 Jul 4;46(1):123–132. doi: 10.1016/0092-8674(86)90866-4. [DOI] [PubMed] [Google Scholar]
- Robbins P. D., Rio D. C., Botchan M. R. trans Activation of the simian virus 40 enhancer. Mol Cell Biol. 1986 Apr;6(4):1283–1295. doi: 10.1128/mcb.6.4.1283. [DOI] [PMC free article] [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]
- Sarver N., Muschel R., Byrne J. C., Khoury G., Howley P. M. Enhancer-dependent expression of the rat preproinsulin gene in bovine papillomavirus type 1 vectors. Mol Cell Biol. 1985 Dec;5(12):3507–3516. doi: 10.1128/mcb.5.12.3507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmidt A., Rossi P., de Crombrugghe B. Transcriptional control of the mouse alpha 2(I) collagen gene: functional deletion analysis of the promoter and evidence for cell-specific expression. Mol Cell Biol. 1986 Feb;6(2):347–354. doi: 10.1128/mcb.6.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schon E., Evans T., Welsh J., Efstratiadis A. Conformation of promoter DNA: fine mapping of S1-hypersensitive sites. Cell. 1983 Dec;35(3 Pt 2):837–848. doi: 10.1016/0092-8674(83)90116-2. [DOI] [PubMed] [Google Scholar]
- Serfling E., Lübbe A., Dorsch-Häsler K., Schaffner W. Metal-dependent SV40 viruses containing inducible enhancers from the upstream region of metallothionein genes. EMBO J. 1985 Dec 30;4(13B):3851–3859. doi: 10.1002/j.1460-2075.1985.tb04157.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Singh H., Sen R., Baltimore D., Sharp P. A. A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes. Nature. 1986 Jan 9;319(6049):154–158. doi: 10.1038/319154a0. [DOI] [PubMed] [Google Scholar]
- Strehler E. E., Mahdavi V., Periasamy M., Nadal-Ginard B. Intron positions are conserved in the 5' end region of myosin heavy-chain genes. J Biol Chem. 1985 Jan 10;260(1):468–471. [PubMed] [Google Scholar]
- Strehler E. E., Periasamy M., Strehler-Page M. A., Nadal-Ginard B. Myosin light-chain 1 and 3 gene has two structurally distinct and differentially regulated promoters evolving at different rates. Mol Cell Biol. 1985 Nov;5(11):3168–3182. doi: 10.1128/mcb.5.11.3168. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strehler E. E., Strehler-Page M. A., Perriard J. C., Periasamy M., Nadal-Ginard B. Complete nucleotide and encoded amino acid sequence of a mammalian myosin heavy chain gene. Evidence against intron-dependent evolution of the rod. J Mol Biol. 1986 Aug 5;190(3):291–317. doi: 10.1016/0022-2836(86)90003-3. [DOI] [PubMed] [Google Scholar]
- Swynghedauw B. Developmental and functional adaptation of contractile proteins in cardiac and skeletal muscles. Physiol Rev. 1986 Jul;66(3):710–771. doi: 10.1152/physrev.1986.66.3.710. [DOI] [PubMed] [Google Scholar]
- Theisen M., Stief A., Sippel A. E. The lysozyme enhancer: cell-specific activation of the chicken lysozyme gene by a far-upstream DNA element. EMBO J. 1986 Apr;5(4):719–724. doi: 10.1002/j.1460-2075.1986.tb04273.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker M. D., Edlund T., Boulet A. M., Rutter W. J. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. doi: 10.1038/306557a0. [DOI] [PubMed] [Google Scholar]
- Weydert A., Daubas P., Caravatti M., Minty A., Bugaisky G., Cohen A., Robert B., Buckingham M. Sequential accumulation of mRNAs encoding different myosin heavy chain isoforms during skeletal muscle development in vivo detected with a recombinant plasmid identified as coding for an adult fast myosin heavy chain from mouse skeletal muscle. J Biol Chem. 1983 Nov 25;258(22):13867–13874. [PubMed] [Google Scholar]
- Weydert A., Daubas P., Lazaridis I., Barton P., Garner I., Leader D. P., Bonhomme F., Catalan J., Simon D., Guénet J. L. Genes for skeletal muscle myosin heavy chains are clustered and are not located on the same mouse chromosome as a cardiac myosin heavy chain gene. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7183–7187. doi: 10.1073/pnas.82.21.7183. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whalen R. G., Sell S. M., Butler-Browne G. S., Schwartz K., Bouveret P., Pinset-Härstöm I. Three myosin heavy-chain isozymes appear sequentially in rat muscle development. Nature. 1981 Aug 27;292(5826):805–809. doi: 10.1038/292805a0. [DOI] [PubMed] [Google Scholar]
- Wieczorek D. F., Periasamy M., Butler-Browne G. S., Whalen R. G., Nadal-Ginard B. Co-expression of multiple myosin heavy chain genes, in addition to a tissue-specific one, in extraocular musculature. J Cell Biol. 1985 Aug;101(2):618–629. doi: 10.1083/jcb.101.2.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wydro R. M., Nguyen H. T., Gubits R. M., Nadal-Ginard B. Characterization of sarcomeric myosin heavy chain genes. J Biol Chem. 1983 Jan 10;258(1):670–678. [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]
- Zakut R., Shani M., Givol D., Neuman S., Yaffe D., Nudel U. Nucleotide sequence of the rat skeletal muscle actin gene. Nature. 1982 Aug 26;298(5877):857–859. doi: 10.1038/298857a0. [DOI] [PubMed] [Google Scholar]