Transcriptional activation of the utrophin promoter B by a constitutively active Ets-transcription factor.

Details

Serval ID
serval:BIB_15A0BA693E7A
Type
Article: article from journal or magazin.
Collection
Publications
Title
Transcriptional activation of the utrophin promoter B by a constitutively active Ets-transcription factor.
Journal
Neuromuscular Disorders
Author(s)
Briguet A., Bleckmann D., Bettan M., Mermod N., Meier T.
ISSN
0960-8966[print], 0960-8966[linking]
Publication state
Published
Issued date
02/2003
Volume
13
Number
2
Pages
143-150
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Duchenne muscular dystrophy is an X-linked genetic disease caused by the absence of functional dystrophin. Pharmacological upregulation of utrophin, the autosomal homologue of dystrophin, offers a potential therapeutic approach to treat Duchenne patients. Full-length utrophin mRNA is transcribed from two alternative promoters, called A and B. In contrast to the utrophin promoter A, little is known about the factors regulating the activity of the utrophin promoter B. Computer analysis of this second promoter revealed the presence of several conserved binding motives for Ets-transcription factors. Using electrotransfer of cDNA into mouse muscles, we demonstrate that a genetically modified beta-subunit of the Ets-transcription factor GA-binding protein potently activates a utrophin promoter B reporter construct in innervated muscle fibers in vivo. These results make the GA-binding protein and the signaling cascade regulating its activity in muscle cells, potential targets for the pharmacological modulation of utrophin expression in Duchenne patients.
Keywords
Amino Acid Motifs/physiology, Animals, Binding Sites, Blotting, Western, CHO Cells, Cell Line, Cell Nucleus/metabolism, Creatine Kinase/metabolism, Creatine Kinase, MM Form, Cricetinae, Cytoplasm/metabolism, Cytoskeletal Proteins/classification, Cytoskeletal Proteins/genetics, DNA-Binding Proteins/classification, DNA-Binding Proteins/genetics, GA-Binding Protein Transcription Factor, Gene Expression Regulation, Isoenzymes/metabolism, Membrane Proteins/classification, Membrane Proteins/genetics, Mice, Molecular Sequence Data, Mutation, Myoblasts/metabolism, Neural Cell Adhesion Molecules/metabolism, Neuregulin-1/metabolism, Plasmids/metabolism, Promoter Regions, Genetic/genetics, Protein Subunits/classification, Protein Subunits/metabolism, RNA, Messenger/biosynthesis, Receptors, Cholinergic/genetics, Receptors, Cholinergic/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Nucleic Acid, Transcription Factors/classification, Transcription Factors/genetics, Transcriptional Activation, Transfection/methods, Up-Regulation, Utrophin, alpha Karyopherins/metabolism
Pubmed
Web of science
Create date
24/01/2008 11:41
Last modification date
20/08/2019 13:44
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