Back to Search
Start Over
Molecular and Functional Analysis of the Utrophin Promoter
- Source :
- Nucleic Acids Research. 24:1646-1652
- Publication Year :
- 1996
- Publisher :
- Oxford University Press (OUP), 1996.
-
Abstract
- 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.
- Subjects :
- Transcription, Genetic
Utrophin
Sp1 Transcription Factor
Sequence analysis
animal diseases
Duchenne muscular dystrophy
Molecular Sequence Data
Cell Line
Conserved sequence
Mice
Exon
Genetics
Transcriptional regulation
medicine
Animals
Humans
RNA, Messenger
Cloning, Molecular
Promoter Regions, Genetic
Conserved Sequence
Sequence Deletion
Binding Sites
Base Sequence
biology
Membrane Proteins
Promoter
Exons
Sequence Analysis, DNA
musculoskeletal system
medicine.disease
Cell biology
Cytoskeletal Proteins
biology.protein
CpG Islands
Dystrophin
Research Article
Subjects
Details
- ISSN :
- 13624962 and 03051048
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....1d48bfb3cc1888cc4b00373ef6bfc770