Transcriptional regulation of the human mu opioid receptor (hMOR) gene: Evidence of positive and negative Cis-acting elements in the proximal promoter and presence of a distal promoter

Authors
Citation
Yh. Xu et Lg. Carr, Transcriptional regulation of the human mu opioid receptor (hMOR) gene: Evidence of positive and negative Cis-acting elements in the proximal promoter and presence of a distal promoter, DNA CELL B, 20(7), 2001, pp. 391-402
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
DNA AND CELL BIOLOGY
ISSN journal
1044-5498 → ACNP
Volume
20
Issue
7
Year of publication
2001
Pages
391 - 402
Database
ISI
SICI code
1044-5498(200107)20:7<391:TROTHM>2.0.ZU;2-R
Abstract
The mu opioid receptor (MOR), the primary binding site for morphine, is an important target for treating pain and drug addiction. The MOR gene is tigh tly regulated at the level of transcription, and potential polymorphisms in its 5' regulatory region can cause individual variation in MOR gene expres sion, nociception, and opiate responses. To study the 5' regulatory region of the human MOR gene (hMOR), we further investigated our previous finding of two regulatory regions and have localized a 40-bp positive cis-acting el ement and a 35-bp negative cis-acting element that regulate hMOR transcript ion in SK-N-SH cells. Electromobility shift assays and methylation interfer ence assay with the 40-bp probe suggested that protein contacts were made w ith the core recognition sequence GCC (-510 to -508). The 35-bp sequence (- 694 to -660) was the hMOR homolog of the mMOR negative regulatory element, and it suppressed proximal promoter activity of the hMOR gene. Additionally , the presence of an hMOR distal promoter was confirmed using RT-PCR. Howev er, the activity of the distal promoter construct (-2325 to -777) was weak compared with the activity of the proximal promoter construct (-776 to -212 ).