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

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Abstract

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.

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References

  • Ahn AH, Kunkel LM (1993) The structural and functional diversity of dystrophin. Nat Genet 3: 283–291

    Google Scholar 

  • 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: 861–863

    Google Scholar 

  • 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: 557–560

    Google Scholar 

  • 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: 17623–17629

    Google Scholar 

  • 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: 1725–1731

    Google Scholar 

  • Byers TJ, Lidov HGW, Kunkel LM (1993) An alternative dystrophin transcript specific to peripheral nerve. Nat Genet 4: 77–81

    Google Scholar 

  • 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: 64–65

    Google Scholar 

  • Chirgwin JM, Przybukla AE, MacDonald RJ, Rutter WJ (1979) Isolation of biologically active ribonucleic acid from sources rich in ribonucleases. Biochemistry 13: 2633–2637

    Google Scholar 

  • Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159

    Google Scholar 

  • Clemens P, Caskey C (1992) Duchenne muscular dystrophy. In: Current neurology. St. Louis, Mosby-Year Book, 20: 1–22

    Google Scholar 

  • 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: 837–842

    Google Scholar 

  • Emery AEH (1987) Duchenne muscular dystrophy. (Oxford monographs on medical genetics, no 15) Oxford, Oxford University Press

    Google Scholar 

  • Ervasti JM, Campbell KP (1991) Membrane organization of the dystrophin-glycoprotein complex. Cell 66: 1121–1131

    Google Scholar 

  • Feener CA, Koenig M, Kunkel LM (1989) Alternative splicing of human dystrophin mRNA generates isoforms at the carboxy terminus. Nature 338: 509–511

    Google Scholar 

  • 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: 123–133

    Google Scholar 

  • 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: 505–510

    Google Scholar 

  • Hammond RG (1987) Protein sequence of DMD gene is related to actin-binding domain of α-actinin. Cell 51: 1

    Google Scholar 

  • Hoffman EP, Hudecki MS, Rosenberg PA, Pollina CM, Kunkel LM (1988) Cell and fibre type distribution of dystrophin. Neuron 1:411–420

    Google Scholar 

  • 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 9:1603–1614

    Google Scholar 

  • 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: 193–205

    Google Scholar 

  • Koenig M, Monaco AP, Kunkel LM (1988) The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53: 219–226

    Google Scholar 

  • Kunkel LM, et al. (1986) Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy. Nature 322: 73–77

    Google Scholar 

  • Lidov HGW, Byers TJ, Watkins SC, Kunkel LM (1990) Localization of dystrophin to post synaptic regions of central nervous system cortical neurons. Nature 348: 725–728

    Google Scholar 

  • Lidov HGW, Selig S, Kunkel LM (1995) Dp 140: a novel 140 kDa CNS transcript from the dystrophin locus. Hum Mol Genet 4: 329–335

    Google Scholar 

  • 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: 496–503

    Google Scholar 

  • 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: 425–438

    Google Scholar 

  • 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: 19463–19470

    Google Scholar 

  • 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: 921–925

    Google Scholar 

  • 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: 151–157

    Google Scholar 

  • 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: 1037–1042

    Google Scholar 

  • 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: 76–78

    Google Scholar 

  • 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: 4497–4505

    Google Scholar 

  • 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: 437–441

    Google Scholar 

  • Roberts R, Bentley D, Bobrow M (1993) Infidelity in the structure of ectopic transcripts: a novel exon in lymphocyte dystrophin transcripts. Hum Mutat 2: 293–299

    Google Scholar 

  • Senter L, Ceoldo S, Meznaric Petruza M, Salviati G (1995) Phosphorylation of dystrophin: effects on actin binding. Biochem Biophys Res Commun 206: 57–63

    Google Scholar 

  • Tamura T, Yoshioka K, Jinno Y, Niikawa N, Miike T (1993) Dystrophin isoforms expressed in the mouse retina. J Neurol Sci 115: 214–218

    Google Scholar 

  • 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: 158–166

    Google Scholar 

  • 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: 1161–1166

    Google Scholar 

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Holder, E., Maeda, M. & Bies, R.D. Expression and regulation of the dystrophin Purkinje promoter in human skeletal muscle, heart, and brain. Hum Genet 97, 232–239 (1996). https://doi.org/10.1007/BF02265272

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  • DOI: https://doi.org/10.1007/BF02265272

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