title: A novel muscle-specific enhancer identified within the deletion overlap region of two XLDC patients lacking muscle exon 1 of the human dystrophin gene.
abstract: Previous studies point to the involvement of several discrete transcriptional enhancers in the modulation of dystrophin gene expression in skeletal and cardiac muscle. Analysis of deletion breakpoints in two X-linked dilated cardiomyopathy patients with mutations that remove muscle exon 1 identified a 3.2-kb deletion overlap region (XLDC3.2) between -1199 and +2057 bp predicted to contain regulatory elements essential for dystrophin gene expression in cardiac muscle. A novel-sequence-based search strategy was used to identify a 543-bp region downstream of muscle exon 1 rich in cardiac-specific transcriptional elements. Designated dystrophin muscle enhancer 2 (DME2), this candidate enhancer was seen to function in a position- and orientation-independent manner in muscle cell lines but not in fibroblasts. As only modest activity was observed in primary neonatal rat cardiomyocytes, DME2 is thought to play a role in dystrophin gene regulation at later stages of cardiac muscle development.
authors.affiliation: Ontario Cancer Institute, Princess Margaret Hospital, Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada.
authors.forename: Carlo
authors.initials: C
authors.lastname: Bastianutto
authors.forename: Marianne
authors.initials: M
authors.lastname: De Visser
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Klamut
authors.forename: Tomaso
authors.initials: T
authors.lastname: Patarnello
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D002460:Cell Line; D016189:Dystrophin / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D008040:Genetic Linkage; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014162:Transfection; D014960:X Chromosome / Q000235:genetics*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D016189:Dystrophin; D011993:Recombinant Fusion Proteins; D008156:Luciferases; D001616:beta-Galactosidase