Human Genetics

, Volume 97, Issue 2, pp 232–239 | Cite as

Expression and regulation of the dystrophin Purkinje promoter in human skeletal muscle, heart, and brain

  • Emma Holder
  • Masato Maeda
  • Roger D. Bies
Original Investigation


Dystrophin mRNA transcripts from the P (Purkinje) promoter were shown to be differentially expressed in human skeletal muscle, heart, and brain. The expression pattern was characteristic of tissue type and developmental stage. Polymerase chain reaction (PCR) analysis of the P promoter transcripts in adult skeletal muscle and adult brain identified two alternatively spliced sequences, one that encodes a full-length dystrophin mRNA and a second that transcribes a termination codon 27 nucleotides (8 amino acids) after the ATG initiation site. Alternative splicing of this truncated coding transcript was developmentally regulated, and it was expressed as the major form in adult cortical brain and adult heart. The biological significance of this peptide remains unclear. The full-length transcript was the major form in fetal cortical brain and adult skeletal muscle. Ribonuclease protection assay demonstrated that as much as 20% of dystrophin transcription in normal adult skeletal muscle was derived from the full-length transcript from the P promoter. In contrast, adult heart did not express significant levels of P promoter derived transcripts. Thus, transcripts from the P promoter were found to be developmentally regulated in the brain, and its activity was differentially expressed in skeletal verses cardiac muscle tissues. These data show that the P promoter transcript displays a broader scope of expression, regulation, and complexity than previously appreciated.


Skeletal Muscle Alternative Splice Verse Human Skeletal Muscle Major Form 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ahn AH, Kunkel LM (1993) The structural and functional diversity of dystrophin. Nat Genet 3: 283–291Google Scholar
  2. Arahata K, Ishiura S, Ishiguro T, Tsukahara T, Suhara Y, Eguchi C, Ishihara T, Nonaka I, Ozawa E, Sugita H (1988) Immunostaining of skeletal and cardiac muscle surface membrane with antibody against Duchenne muscular dystrophy peptide. Nature 333: 861–863Google Scholar
  3. Bar S, Barnea E, Levy Z, Neuman S, Yaffe D, Nudel U (1990) A novel product of the human dystrophin gene which greatly differs from the known isoforms in its structure and tissue distribution. Biochem J 272: 557–560Google Scholar
  4. Baron MD, Davison MD, Jones P, Critchley DR (1987) The sequence of chick alpha-actinin reveals homologies to spectrin and calmodulin. J Biol Chem 262: 17623–17629Google Scholar
  5. Bies RD, Phelps SF, Roberts R, Caskey CT, Chamberlain JS (1992) Human and murine dystrophin mRNA transcripts are differentially expressed during skeletal muscle, heart and brain development. Nucleic Acids Res 20: 1725–1731Google Scholar
  6. Byers TJ, Lidov HGW, Kunkel LM (1993) An alternative dystrophin transcript specific to peripheral nerve. Nat Genet 4: 77–81Google Scholar
  7. Chelly J, Hamard G, Koulakoff A, Kaplan J, Kahn A, BerwaldNetter Y (1990) Dystrophin gene transcribed from different promoters in neuronal and glial cells. Nature 344: 64–65Google Scholar
  8. Chirgwin JM, Przybukla AE, MacDonald RJ, Rutter WJ (1979) Isolation of biologically active ribonucleic acid from sources rich in ribonucleases. Biochemistry 13: 2633–2637Google Scholar
  9. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159Google Scholar
  10. Clemens P, Caskey C (1992) Duchenne muscular dystrophy. In: Current neurology. St. Louis, Mosby-Year Book, 20: 1–22Google Scholar
  11. D'Souza VN, Man N, Morris GE, Karges W, Pillers DM, Ray PN (1995) A novel dystrophin isoform is required for normal retinal electrophysiology. Hum Mol Genet 4: 837–842Google Scholar
  12. Emery AEH (1987) Duchenne muscular dystrophy. (Oxford monographs on medical genetics, no 15) Oxford, Oxford University PressGoogle Scholar
  13. Ervasti JM, Campbell KP (1991) Membrane organization of the dystrophin-glycoprotein complex. Cell 66: 1121–1131Google Scholar
  14. Feener CA, Koenig M, Kunkel LM (1989) Alternative splicing of human dystrophin mRNA generates isoforms at the carboxy terminus. Nature 338: 509–511Google Scholar
  15. Geng Y, Sicinski P, Gorecki DC, Barnard PJ (1991) Development and tissue-specific regulation of mouse dystrophin: the embryonic isoform in muscular dystrophin. Neuromusc Disord 1: 123–133Google Scholar
  16. Gorecki DC, Monaco AP, Derry JMJ, Walker AP, Barnard EA, Barnard PJ (1992) Expression of four alternative dystrophin transcripts in brain regions regulated by different promoters Hum Mol Genet 1: 505–510Google Scholar
  17. Hammond RG (1987) Protein sequence of DMD gene is related to actin-binding domain of α-actinin. Cell 51: 1Google Scholar
  18. Hoffman EP, Hudecki MS, Rosenberg PA, Pollina CM, Kunkel LM (1988) Cell and fibre type distribution of dystrophin. Neuron 1:411–420Google Scholar
  19. Kastner P, Kurst A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P (1990) Two distinct estrogen-related promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J 9:1603–1614Google Scholar
  20. Klamut HJ, Gangopadhyay SB, Worton RG, Ray PN (1990) Molecular and functional analysis of the muscle specific promoter region of the Duchenne muscular dystrophy gene. Mol Cell Biol 10: 193–205Google Scholar
  21. Koenig M, Monaco AP, Kunkel LM (1988) The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53: 219–226Google Scholar
  22. Kunkel LM, et al. (1986) Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy. Nature 322: 73–77Google Scholar
  23. Lidov HGW, Byers TJ, Watkins SC, Kunkel LM (1990) Localization of dystrophin to post synaptic regions of central nervous system cortical neurons. Nature 348: 725–728Google Scholar
  24. Lidov HGW, Selig S, Kunkel LM (1995) Dp 140: a novel 140 kDa CNS transcript from the dystrophin locus. Hum Mol Genet 4: 329–335Google Scholar
  25. Lindlof M, Kiurn A, Kaariainen H, Kalimo H, Lang H, Pihko H, Rapola J, Somer H, Somer M, Savontaus ML (1989) Gene deletions in X-linked muscular dystrophy. Am J Hum Genet 44: 496–503Google Scholar
  26. Maire P, Gautron S, Hakim V, Gregori C, Mennecier F, Kahn A (1987) Characterization of three optimal promoters in the 5′ region of the human aldolase gene. J Mol Biol 197: 425–438Google Scholar
  27. Mahendroo MS, Mendelson CR, Simpson ER (1993) Tissue-specific and hormonal alternative promotors regulate aromatase cytochrome P450 gene expression in human adipose tissue. J Biol Chem 268: 19463–19470Google Scholar
  28. Muntoni F, Cau M, Ganau A, Congiu R, Arvedi G, Mateddu A, Marrosu M, Cianchetti C, Realdi G, Cao A, Melis M (1993) Deletion of the muscle-promoter region associated with Xlinked dilated cardiomyopathy. N Engl J Med 329: 921–925Google Scholar
  29. Muntoni F, Melis MA, Ganau A, Dubowitz V (1995) Transcription of the dystrophin gene in normal tissues and in skeletal muscle of a family with X-linked dilated cardiomyopathy. Am J Hum Genet 56: 151–157Google Scholar
  30. Nishio H, Takeshima Y, Narita N, Yanagawa H, Suzuki Y, Ishikawa Y, Ishikawa Y, Minami R, Nakamura H, Matsuo M (1994) Identification of a novel first exon in the human dystrophin gene and of a new promoter located more than 500 kb upstream of the nearest known promoter. J Clin Invest 94: 1037–1042Google Scholar
  31. Nudel U, Zuk D, Einat P, Zeelon E, Levy Z, Neuman S, Yaffe D (1989) Duchenne muscular dystrophy gene product is not identical in muscle and brain. Nature 337: 76–78Google Scholar
  32. Parola A, Koblika B (1994) The peptide product of a 5' leader cistron in the β2 adrenergic receptor mRNA inhibits receptor synthesis. J Biol Chem 269: 4497–4505Google Scholar
  33. Rapaport D, Passos-Bueno MR, Brandao L, Love D, Vainzof M, Zatz M (1991) Apparent association of mental retardation and specific patterns of deletions screened with probes cf56a and cf23a in Duchenne muscular dystrophy. Am J Hum Genet 39: 437–441Google Scholar
  34. Roberts R, Bentley D, Bobrow M (1993) Infidelity in the structure of ectopic transcripts: a novel exon in lymphocyte dystrophin transcripts. Hum Mutat 2: 293–299Google Scholar
  35. Senter L, Ceoldo S, Meznaric Petruza M, Salviati G (1995) Phosphorylation of dystrophin: effects on actin binding. Biochem Biophys Res Commun 206: 57–63Google Scholar
  36. Tamura T, Yoshioka K, Jinno Y, Niikawa N, Miike T (1993) Dystrophin isoforms expressed in the mouse retina. J Neurol Sci 115: 214–218Google Scholar
  37. Winnard AV, Mendell JR, Prior TW, Florence J, Burghes AHM (1995) Frameshift deletions of exons 3-7 and revertant fibers in Duchenne Muscular Dystrophy: mechanism of dystrophin production. Am J Hum Genet 36: 158–166Google Scholar
  38. Yoshida K, Ikeda S, Nakamure A, Kagoshima M, Takeda S, Shoji S, Yanagisawa (1993) Molecular analysis of the Duchenne muscular dystrophy gene in patients with Becker muscular dystrophy presenting with dilated cardiomyopathy. Muscle Nerve 16: 1161–1166Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Emma Holder
    • 1
  • Masato Maeda
    • 1
  • Roger D. Bies
    • 1
  1. 1.Cardiology Division, Temple Hoyne Buell LaboratoriesUniversity of Colorado Health Sciences Center and the VA Medical CenterDenverUSA

Personalised recommendations