Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (119K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (59)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Dennis, C.
Right arrow Articles by Davies, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dennis, C.
Right arrow Articles by Davies, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, Vol 24, Issue 9 1646-1652, Copyright © 1996 by Oxford University Press

ARTICLES

Molecular and functional analysis of the utrophin promoter

CL Dennis, JM Tinsley, AE Deconinck and KE Davies
Department of Biochemistry, University of Oxford, UK.

Utrophin is a ubiquitously expressed cytoskeletal protein which is an important structural component of the mammalian neuromuscular junction. It shows extensive sequence similarity to dystrophin leading to postulation that utrophin may be able to compensate for the absence of dystrophin in Duchenne muscular dystrophy (DMD) patients. In order to study the transcriptional control of utrophin expression including its regulation at the neuromuscular junction, and as a first step in the development of a potential DMD therapy, we have cloned the utrophin promoter region from human and mouse. The utrophin promoter is associated with a CpG island at the 5'-end of the gene, and sequence analysis of the 5'-UTR reveals several Sp1 binding sites and the absence of TATA or CAAT motifs. Transcription is initiated at one major and three minor sites. Using deletion constructs, we have defined an active promoter region of 155 bp. The first exon and 900 bp upstream display limited sequence conservation between human and mouse. The core sequence TTCCGG of the N box which regulates synaptic expression of other genes is also present and may be involved in regulating the specific expression of utrophin at the postsynaptic membrane. This study provides the basis for the understanding of the regulatory mechanism that controls utrophin expression and provides the data needed to develop methods for the upregulation of utrophin in DMD patients.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
P. Miura, J. V. Chakkalakal, L. Boudreault, G. Belanger, R. L. Hebert, J.-M. Renaud, and B. J. Jasmin
Pharmacological activation of PPAR{beta}/{delta} stimulates utrophin A expression in skeletal muscle fibers and restores sarcolemmal integrity in mature mdx mice
Hum. Mol. Genet., December 1, 2009; 18(23): 4640 - 4649.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Lu, C. Tian, G. Danialou, R. Gilbert, B. J. Petrof, G. Karpati, and J. Nalbantoglu
Targeting Artificial Transcription Factors to the Utrophin A Promoter: EFFECTS ON DYSTROPHIC PATHOLOGY AND MUSCLE FUNCTION
J. Biol. Chem., December 12, 2008; 283(50): 34720 - 34727.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
K. J. Perkins, U. Basu, M. T. Budak, C. Ketterer, S. M. Baby, O. Lozynska, J. A. Lunde, B. J. Jasmin, N. A. Rubinstein, and T. S. Khurana
Ets-2 Repressor Factor Silences Extrasynaptic Utrophin by N-Box mediated Repression in Skeletal Muscle
Mol. Biol. Cell, August 1, 2007; 18(8): 2864 - 2872.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Miura, J. Thompson, J. V. Chakkalakal, M. Holcik, and B. J. Jasmin
The Utrophin A 5'-Untranslated Region Confers Internal Ribosome Entry Site-mediated Translational Control during Regeneration of Skeletal Muscle Fibers
J. Biol. Chem., September 23, 2005; 280(38): 32997 - 33005.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. B. de Leon, C. Montanez, P. Gomez, S. L. Morales-Lazaro, V. Tapia-Ramirez, V. Valadez-Graham, F. Recillas-Targa, D. Yaffe, U. Nudel, and B. Cisneros
Dystrophin Dp71 Expression Is Down-regulated during Myogenesis: ROLE OF Sp1 AND Sp3 ON THE Dp71 PROMOTER ACTIVITY
J. Biol. Chem., February 18, 2005; 280(7): 5290 - 5299.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. O. B. Krag, S. Bogdanovich, C. J. Jensen, M. D. Fischer, J. Hansen-Schwartz, E. H. Javazon, A. W. Flake, L. Edvinsson, and T. S. Khurana
Heregulin ameliorates the dystrophic phenotype in mdx mice
PNAS, September 21, 2004; 101(38): 13856 - 13860.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Galvagni, M. Cantini, and S. Oliviero
The Utrophin Gene Is Transcriptionally Up-regulated in Regenerating Muscle
J. Biol. Chem., May 17, 2002; 277(21): 19106 - 19113.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
D. J. Blake, A. Weir, S. E. Newey, and K. E. Davies
Function and Genetics of Dystrophin and Dystrophin-Related Proteins in Muscle
Physiol Rev, April 1, 2002; 82(2): 291 - 329.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
K. J. Perkins, E. A. Burton, and K. E. Davies
The role of basal and myogenic factors in the transcriptional activation of utrophin promoter A: implications for therapeutic up-regulation in Duchenne muscular dystrophy
Nucleic Acids Res., December 1, 2001; 29(23): 4843 - 4850.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Galvagni and S. Oliviero
Utrophin Transcription Is Activated by an Intronic Enhancer
J. Biol. Chem., February 4, 2000; 275(5): 3168 - 3172.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
E. A. Burton, J. M. Tinsley, P. J. Holzfeind, N. R. Rodrigues, and K. E. Davies
A second promoter provides an alternative target for therapeutic up-regulation of utrophin in Duchenne muscular dystrophy
PNAS, November 23, 1999; 96(24): 14025 - 14030.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
T. S. Khurana, A. G. Rosmarin, J. Shang, T. O. B. Krag, S. Das, and S. Gammeltoft
Activation of Utrophin Promoter by Heregulin via the ets-related Transcription Factor Complex GA-binding Protein alpha /beta
Mol. Biol. Cell, June 1, 1999; 10(6): 2075 - 2086.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
A. O. Gramolini, E. A. Burton, J. M. Tinsley, M. J. Ferns, A. Cartaud, J. Cartaud, K. E. Davies, J. A. Lunde, and B. J. Jasmin
Muscle and Neural Isoforms of Agrin Increase Utrophin Expression in Cultured Myotubes via a Transcriptional Regulatory Mechanism
J. Biol. Chem., January 9, 1998; 273(2): 736 - 743.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
J. Porter, J. Rafael, R. Ragusa, J. Brueckner, J. Trickett, and K. Davies
The sparing of extraocular muscle in dystrophinopathy is lost in mice lacking utrophin and dystrophin
J. Cell Sci., January 7, 1998; 111(13): 1801 - 1811.
[Abstract] [PDF]

Home page
 J. Biol. Chem.Home page
A. O. Gramolini, C. L. Dennis, J. M. Tinsley, G. S. Robertson, J. Cartaud, K. E. Davies, and B. J. Jasmin
Local Transcriptional Control of Utrophin Expression at the Neuromuscular Synapse
J. Biol. Chem., March 28, 1997; 272(13): 8117 - 8120.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
A. E. Deconinck, A. C. Potter, J. M. Tinsley, S. J. Wood, R. Vater, C. Young, L. Metzinger, A. Vincent, C. R. Slater, and K. E. Davies
Postsynaptic Abnormalities at the Neuromuscular Junctions of Utrophin-deficient Mice
J. Cell Biol., February 24, 1997; 136(4): 883 - 894.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.