HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Storbeck, C. J. Articles by Korneluk, R. G. Search for Related Content PubMed PubMed Citation Articles by Storbeck, C. J. Articles by Korneluk, R. G. Social Bookmarking                      What's this?

J Biol Chem, Vol. 273, Issue 15, 9139-9147, April 10, 1998

Definition of Regulatory Sequence Elements in the Promoter Region and the First Intron of the Myotonic Dystrophy Protein Kinase Gene

Chris J. Storbeck, Luc A. Sabourin, James D. Waring, and Robert G. Korneluk

From the  Department of Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada and the  Solange Gauthier Karsh Molecular Genetics Laboratory, Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada

Myotonic dystrophy is the most common inherited adult neuromuscular disorder with a global frequency of 1/8000. The genetic defect is an expanding CTG trinucleotide repeat in the 3'-untranslated region of the myotonic dystrophy protein kinase gene. We present the in vitro characterization of cis regulatory elements controlling transcription of the myotonic dystrophy protein kinase gene in myoblasts and fibroblasts. The region 5' to the initiating ATG contains no consensus TATA or CCAAT box. We have mapped two transcriptional start sites by primer extension. Deletion constructs from this region fused to the bacterial chloramphenicol acetyltransferase reporter gene revealed only subtle muscle specific cis elements. The strongest promoter activity mapped to a 189-base pair fragment. This sequence contains a conserved GC box to which the transcription factor Sp1 binds. Reporter gene constructs containing a 2-kilobase pair first intron fragment of the myotonic dystrophy protein kinase gene enhances reporter activity up to 6-fold in the human rhabdomyosarcoma myoblast cell line TE32 but not in NIH 3T3 fibroblasts. Co-transfection of a MyoD expression vector with reporter constructs containing the first intron into 10 T1/2 fibroblasts resulted in a 10-20-fold enhancement of expression. Deletion analysis of four E-box elements within the first intron reveal that these elements contribute to enhancer activity similarly in TE32 myoblasts and 10 T1/2 fibroblasts. These data suggest that E-boxes within the myotonic dystrophy protein kinase first intron mediate interactions with upstream promoter elements to up-regulate transcription of this gene in myoblasts.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				D. F. O'Cochlain, C. Perez-Terzic, S. Reyes, G. C. Kane, A. Behfar, D. M. Hodgson, J. A. Strommen, X.-K. Liu, W. van den Broek, D. G. Wansink, et al. Transgenic overexpression of human DMPK accumulates into hypertrophic cardiomyopathy, myotonic myopathy and hypotension traits of myotonic dystrophy Hum. Mol. Genet., October 1, 2004; 13(20): 2505 - 2518. [Abstract] [Full Text] [PDF]

				C. J. Storbeck, S. Drmanic, K. Daniel, J. D. Waring, F. R. Jirik, D. J. Parry, N. Ahmed, L. A. Sabourin, J.-E Ikeda, and R. G. Korneluk Inhibition of myogenesis in transgenic mice expressing the human DMPK 3'-UTR Hum. Mol. Genet., March 15, 2004; 13(6): 589 - 600. [Abstract] [Full Text] [PDF]

				D. Furling, L. T. Lam, O. Agbulut, G. S. Butler-Browne, and G. E. Morris Changes in Myotonic Dystrophy Protein Kinase Levels and Muscle Development in Congenital Myotonic Dystrophy Am. J. Pathol., March 1, 2003; 162(3): 1001 - 1009. [Abstract] [Full Text] [PDF]

				M. Carrasco, J. Canicio, M. Palacin, A. Zorzano, and P. Kaliman Identification of Intracellular Signaling Pathways that Induce Myotonic Dystrophy Protein Kinase Expression during Myogenesis Endocrinology, August 1, 2002; 143(8): 3017 - 3025. [Abstract] [Full Text] [PDF]