• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Cell Biol. Apr 2, 1995; 129(2): 383–396.
PMCID: PMC2199907

Myosin light chain 3F regulatory sequences confer regionalized cardiac and skeletal muscle expression in transgenic mice

Abstract

The myosin light chain IF/3F locus contains two independent promoters, MLC1F and MLC3F, which are differentially activated during skeletal muscle development. Transcription at this locus is regulated by a 3' skeletal muscle enhancer element, which directs correct temporal and tissue-specific expression from the MLC1F promoter in transgenic mice. To investigate the role of this enhancer in regulation of the MLC3F promoter in vivo, we have analyzed reporter gene expression in transgenic mice containing lacZ under transcriptional control of the mouse MLC3F promoter and 3' enhancer element. Our results show that these regulatory elements direct strong expression of lacZ in skeletal muscle; the transgene, however, is activated 4-5 d before the endogenous MLC3F promoter, at the time of initiation of MLC1F transcription. In adult mice, transgene activity is downregulated in muscles that have reduced contributions of type IIB fibers (soleus and diaphragm). The rostrocaudal positional gradient of transgene expression documented for MLC1F transgenic mice (Donoghue, M., J. P. Merlie, N. Rosenthal, and J. R. Sanes. 1991. Proc. Natl. Acad. Sci. USA. 88:5847-5851) is not seen in MLC3F transgenic mice. Although MLC3F was previously thought to be restricted to skeletal striated muscle, the MLC3F-lacZ transgene is expressed in cardiac muscle from 7.5 d of development in a spatially restricted manner in the atria and left ventricular compartments, suggesting that transcriptional differences exist between cardiomyocytes in left and right compartments of the heart. We show here that transgene-directed expression of the MLC3F promoter reflects low level expression of endogenous MLC3F transcripts in the mouse heart.

Full Text

The Full Text of this article is available as a PDF (11M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • 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. [PMC free article] [PubMed]
  • Barton PJ, Buckingham ME. The myosin alkali light chain proteins and their genes. Biochem J. 1985 Oct 15;231(2):249–261. [PMC free article] [PubMed]
  • Barton PJ, Cohen A, Robert B, Fiszman MY, Bonhomme F, Guénet JL, Leader DP, Buckingham ME. The myosin alkali light chains of mouse ventricular and slow skeletal muscle are indistinguishable and are encoded by the same gene. J Biol Chem. 1985 Jul 15;260(14):8578–8584. [PubMed]
  • Barton PJ, Robert B, Fiszman MY, Leader DP, Buckingham ME. The same myosin alkali light chain gene is expressed in adult cardiac atria and in fetal skeletal muscle. J Muscle Res Cell Motil. 1985 Aug;6(4):461–475. [PubMed]
  • Barton PJ, Harris AJ, Buckingham ME. Myosin light chain gene expression in developing and denervated fetal muscle in the mouse. Development. 1989 Dec;107(4):819–824. [PubMed]
  • Biben C, Kirschbaum BJ, Garner I, Buckingham M. Novel muscle-specific enhancer sequences upstream of the cardiac actin gene. Mol Cell Biol. 1994 May;14(5):3504–3513. [PMC free article] [PubMed]
  • Bottinelli R, Betto R, Schiaffino S, Reggiani C. Unloaded shortening velocity and myosin heavy chain and alkali light chain isoform composition in rat skeletal muscle fibres. J Physiol. 1994 Jul 15;478(Pt 2):341–349. [PMC free article] [PubMed]
  • Brennan TJ, Edmondson DG, Olson EN. Aberrant regulation of MyoD1 contributes to the partially defective myogenic phenotype of BC3H1 cells. J Cell Biol. 1990 Apr;110(4):929–937. [PMC free article] [PubMed]
  • Buckingham M. Making muscle in mammals. Trends Genet. 1992 Apr;8(4):144–148. [PubMed]
  • Cox RD, Buckingham ME. Actin and myosin genes are transcriptionally regulated during mouse skeletal muscle development. Dev Biol. 1992 Jan;149(1):228–234. [PubMed]
  • Dillon N, Grosveld F. Transcriptional regulation of multigene loci: multilevel control. Trends Genet. 1993 Apr;9(4):134–137. [PubMed]
  • Daubas P, Klarsfeld A, Garner I, Pinset C, Cox R, Buckingham M. Functional activity of the two promoters of the myosin alkali light chain gene in primary muscle cell cultures: comparison with other muscle gene promoters and other culture systems. Nucleic Acids Res. 1988 Feb 25;16(4):1251–1271. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Donoghue MJ, Merlie JP, Rosenthal N, Sanes JR. Rostrocaudal gradient of transgene expression in adult skeletal muscle. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5847–5851. [PMC free article] [PubMed]
  • Donoghue MJ, Alvarez JD, Merlie JP, Sanes JR. 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. [PMC free article] [PubMed]
  • Donoghue MJ, Morris-Valero R, Johnson YR, Merlie JP, Sanes JR. Mammalian muscle cells bear a cell-autonomous, heritable memory of their rostrocaudal position. Cell. 1992 Apr 3;69(1):67–77. [PubMed]
  • Donoghue MJ, Patton BL, Sanes JR, Merlie JP. An axial gradient of transgene methylation in murine skeletal muscle: genomic imprint of rostrocaudal position. Development. 1992 Dec;116(4):1101–1112. [PubMed]
  • Faerman A, Shani M. The expression of the regulatory myosin light chain 2 gene during mouse embryogenesis. Development. 1993 Jul;118(3):919–929. [PubMed]
  • Gardner DG, Deschepper CF, Ganong WF, Hane S, Fiddes J, Baxter JD, Lewicki J. Extra-atrial expression of the gene for atrial natriuretic factor. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6697–6701. [PMC free article] [PubMed]
  • Garfinkel LI, Davidson N. Developmentally regulated expression of a truncated myosin light-chain 1F/3F gene. Mol Cell Biol. 1987 Oct;7(10):3826–3829. [PMC free article] [PubMed]
  • Gauthier GF, Lowey S, Benfield PA, Hobbs AW. Distribution and properties of myosin isozymes in developing avian and mammalian skeletal muscle fibers. J Cell Biol. 1982 Feb;92(2):471–484. [PMC free article] [PubMed]
  • Gorza L, Ausoni S, Merciai N, Hastings KE, Schiaffino S. Regional differences in troponin I isoform switching during rat heart development. Dev Biol. 1993 Mar;156(1):253–264. [PubMed]
  • 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. [PubMed]
  • Gundersen K, Sanes JR, Merlie JP. Neural regulation of muscle acetylcholine receptor epsilon- and alpha-subunit gene promoters in transgenic mice. J Cell Biol. 1993 Dec;123(6 Pt 1):1535–1544. [PMC free article] [PubMed]
  • Hall ZW, Sanes JR. Synaptic structure and development: the neuromuscular junction. Cell. 1993 Jan;72 (Suppl):99–121. [PubMed]
  • Hallauer PL, Bradshaw HL, Hastings KE. Complex fiber-type-specific expression of fast skeletal muscle troponin I gene constructs in transgenic mice. Development. 1993 Nov;119(3):691–701. [PubMed]
  • Hoh JF. Developmental changes in chicken skeletal myosin isoenzymes. FEBS Lett. 1979 Feb 15;98(2):267–270. [PubMed]
  • Kalderon D, Roberts BL, Richardson WD, Smith AE. A short amino acid sequence able to specify nuclear location. Cell. 1984 Dec;39(3 Pt 2):499–509. [PubMed]
  • LaFramboise WA, Daood MJ, Guthrie RD, Schiaffino S, Moretti P, Brozanski B, Ontell MP, Butler-Browne GS, Whalen RG, Ontell M. Emergence of the mature myosin phenotype in the rat diaphragm muscle. Dev Biol. 1991 Mar;144(1):1–15. [PubMed]
  • Laird PW, Zijderveld A, Linders K, Rudnicki MA, Jaenisch R, Berns A. Simplified mammalian DNA isolation procedure. Nucleic Acids Res. 1991 Aug 11;19(15):4293–4293. [PMC free article] [PubMed]
  • Lee KJ, Ross RS, Rockman HA, Harris AN, O'Brien TX, van Bilsen M, Shubeita HE, Kandolf R, Brem G, Price J, et al. 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]
  • Lewis DM, Parry DJ, Rowlerson A. Isometric contractions of motor units and immunohistochemistry of mouse soleus muscle. J Physiol. 1982 Apr;325:393–401. [PMC free article] [PubMed]
  • Li Z, Marchand P, Humbert J, Babinet C, Paulin D. Desmin sequence elements regulating skeletal muscle-specific expression in transgenic mice. Development. 1993 Mar;117(3):947–959. [PubMed]
  • Lowey S, Waller GS, Trybus KM. Skeletal muscle myosin light chains are essential for physiological speeds of shortening. Nature. 1993 Sep 30;365(6445):454–456. [PubMed]
  • Lyons GE, Ontell M, Cox R, Sassoon D, Buckingham M. The expression of myosin genes in developing skeletal muscle in the mouse embryo. J Cell Biol. 1990 Oct;111(4):1465–1476. [PMC free article] [PubMed]
  • Lyons GE, Schiaffino S, Sassoon D, Barton P, Buckingham M. Developmental regulation of myosin gene expression in mouse cardiac muscle. J Cell Biol. 1990 Dec;111(6 Pt 1):2427–2436. [PMC free article] [PubMed]
  • McBurney MW, Staines WA, Boekelheide K, Parry D, Jardine K, Pickavance L. Murine PGK-1 promoter drives widespread but not uniform expression in transgenic mice. Dev Dyn. 1994 Aug;200(4):278–293. [PubMed]
  • Merrifield PA, Konigsberg IR. Nerve-dependent accumulation of myosin light chain 3 in developing limb musculature. Development. 1987 Dec;101(4):673–684. [PubMed]
  • 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. [PubMed]
  • Obinata T, Masaki T, Takano-Ohmuro H, Tanaka T, Shimizu N. Coexistence of cardiac-type and fast skeletal-type myosin light chains in embryonic chicken cardiac muscle. J Biochem. 1983 Sep;94(3):1025–1028. [PubMed]
  • O'Brien TX, Lee KJ, Chien KR. Positional specification of ventricular myosin light chain 2 expression in the primitive murine heart tube. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5157–5161. [PMC free article] [PubMed]
  • Pajak L, Mariappan M, Wieczorek DF. Reprogramming of myosin light chain 1/3 expression in muscle heterokaryons. Dev Biol. 1991 May;145(1):28–39. [PubMed]
  • Pette D, Staron RS. Cellular and molecular diversities of mammalian skeletal muscle fibers. Rev Physiol Biochem Pharmacol. 1990;116:1–76. [PubMed]
  • Periasamy M, Strehler EE, Garfinkel LI, Gubits RM, Ruiz-Opazo N, Nadal-Ginard B. Fast skeletal muscle myosin light chains 1 and 3 are produced from a single gene by a combined process of differential RNA transcription and splicing. J Biol Chem. 1984 Nov 10;259(21):13595–13604. [PubMed]
  • Piette J, Huchet M, Houzelstein D, Changeux JP. Compartmentalized expression of the alpha- and gamma-subunits of the acetylcholine receptor in recently fused myofibers. Dev Biol. 1993 May;157(1):205–213. [PubMed]
  • Robert B, Daubas P, Akimenko MA, Cohen A, Garner I, Guenet JL, 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. [PubMed]
  • Rosenthal N. Muscle cell differentiation. Curr Opin Cell Biol. 1989 Dec;1(6):1094–1101. [PubMed]
  • Rosenthal N, Kornhauser JM, Donoghue M, Rosen KM, Merlie JP. 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. [PMC free article] [PubMed]
  • Rosenthal N, Berglund EB, Wentworth BM, Donoghue M, Winter B, Bober E, Braun T, Arnold HH. 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. [PMC free article] [PubMed]
  • Sanes JR, Rubenstein JL, Nicolas JF. Use of a recombinant retrovirus to study post-implantation cell lineage in mouse embryos. EMBO J. 1986 Dec 1;5(12):3133–3142. [PMC free article] [PubMed]
  • Sassoon DA, 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. [PubMed]
  • Sassoon D, Rosenthal N. Detection of messenger RNA by in situ hybridization. Methods Enzymol. 1993;225:384–404. [PubMed]
  • Schiaffino S, Reggiani C. Myosin isoforms in mammalian skeletal muscle. J Appl Physiol (1985) 1994 Aug;77(2):493–501. [PubMed]
  • Seidel U, Arnold HH. 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]
  • Strehler EE, Periasamy M, Strehler-Page MA, 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. [PMC free article] [PubMed]
  • Tajbakhsh S, Vivarelli E, Cusella-De Angelis G, Rocancourt D, Buckingham M, Cossu G. A population of myogenic cells derived from the mouse neural tube. Neuron. 1994 Oct;13(4):813–821. [PubMed]
  • Wada M, Pette D. Relationships between alkali light-chain complement and myosin heavy-chain isoforms in single fast-twitch fibers of rat and rabbit. Eur J Biochem. 1993 May 15;214(1):157–161. [PubMed]
  • Weintraub H. The MyoD family and myogenesis: redundancy, networks, and thresholds. Cell. 1993 Dec 31;75(7):1241–1244. [PubMed]
  • Wentworth BM, Donoghue M, Engert JC, Berglund EB, 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. [PMC free article] [PubMed]
  • Whalen RG, Sell SM, Eriksson A, Thornell LE. Myosin subunit types in skeletal and cardiac tissues and their developmental distribution. Dev Biol. 1982 Jun;91(2):478–484. [PubMed]
  • Wigston DJ, English AW. Fiber-type proportions in mammalian soleus muscle during postnatal development. J Neurobiol. 1992 Feb;23(1):61–70. [PubMed]
  • Yu YT, Breitbart RE, Smoot LB, 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. [PubMed]
  • Zardini DM, Parry DJ. Identification, distribution, and myosin subunit composition of type IIX fibers in mouse muscles. Muscle Nerve. 1994 Nov;17(11):1308–1316. [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...