| First Author | Dennis CL | Year | 1996 |
| Journal | Nucleic Acids Res | Volume | 24 |
| Issue | 9 | Pages | 1646-52 |
| PubMed ID | 8649981 | Mgi Jnum | J:33948 |
| Mgi Id | MGI:81428 | Doi | 10.1093/nar/24.9.1646 |
| Citation | Dennis CL, et al. (1996) Molecular and functional analysis of the utrophin promoter. Nucleic Acids Res 24(9):1646-52 |
| abstractText | 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. |
