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Article

Differential regulation of mouse and human Mu opioid receptor gene depends on the single stranded DNA structure of its promoter and α-complex protein 1

  • Authors:
    • Dong‑Sun Lee
    • Ping‑Yee Law
    • Wei Ln
    • Horace H. Loh
    • Kyu Young Song
    • Hack Sun Choi
  • View Affiliations / Copyright

    Affiliations: Department of Biotechnology, College of Applied Life Science, Jeju National University, Jeju 63243, Republic of Korea, Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
  • Pages: 532-538
    |
    Published online on: March 21, 2017
       https://doi.org/10.3892/br.2017.877
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Abstract

The Mu opioid receptor (MOR) mediates various functions of opioid-induced analgesia, euphoria and respiratory depression, and is a major target of opioid analgesics. Understanding of MOR gene expression among species is important for understanding its analgesic function in humans. In the current study, the polypyrimidine/polypurine (PPy/u) region, a key element of MOR gene expression, was compared in humans and mice. The mouse PPy/u element is highly homologous to its human element (84%), and the mouse MOR (mMOR) reporter drives luciferase activity 35‑fold more effectively than the human MOR (hMOR) reporter. The structural study of reporter plasmids using S1 nuclease indicates that the mouse PPy/u element has a particular conformational structure, namely a single‑stranded DNA (ssDNA) region that promotes strong promoter activity. DNA electrophoretic mobility shift assays demonstrated that the recombinant α‑complex protein 1 (α‑CP1) is capable of binding to a single‑stranded mouse PPy/u sequence. Furthermore, plasmid‑expressing α‑CP1 activated the expression of a luciferase reporter when cotransfected with a single‑stranded (p336/306) construct. In addition, the α‑CP1 gene induced the mMOR gene in mouse neuronal cells and did not induce the human neuronal MOR gene. The current study demonstrates that α‑CP1 functions as a transcriptional activator in the mMOR gene, but does not function in the hMOR gene due to species‑specific structural differences. The differences in human and mouse MOR gene expression are based on α‑CP1 and the ssDNA structure of the MOR promoter. The MOR gene is species‑specifically regulated, as the PPy/u element adopts a unique species-specific conformation and α-CP1 recruitment.
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Copy and paste a formatted citation
Spandidos Publications style
Lee DS, Law PY, Ln W, Loh HH, Song KY and Choi HS: Differential regulation of mouse and human Mu opioid receptor gene depends on the single stranded DNA structure of its promoter and α-complex protein 1. Biomed Rep 6: 532-538, 2017.
APA
Lee, D., Law, P., Ln, W., Loh, H.H., Song, K.Y., & Choi, H.S. (2017). Differential regulation of mouse and human Mu opioid receptor gene depends on the single stranded DNA structure of its promoter and α-complex protein 1. Biomedical Reports, 6, 532-538. https://doi.org/10.3892/br.2017.877
MLA
Lee, D., Law, P., Ln, W., Loh, H. H., Song, K. Y., Choi, H. S."Differential regulation of mouse and human Mu opioid receptor gene depends on the single stranded DNA structure of its promoter and α-complex protein 1". Biomedical Reports 6.5 (2017): 532-538.
Chicago
Lee, D., Law, P., Ln, W., Loh, H. H., Song, K. Y., Choi, H. S."Differential regulation of mouse and human Mu opioid receptor gene depends on the single stranded DNA structure of its promoter and α-complex protein 1". Biomedical Reports 6, no. 5 (2017): 532-538. https://doi.org/10.3892/br.2017.877
Copy and paste a formatted citation
x
Spandidos Publications style
Lee DS, Law PY, Ln W, Loh HH, Song KY and Choi HS: Differential regulation of mouse and human Mu opioid receptor gene depends on the single stranded DNA structure of its promoter and α-complex protein 1. Biomed Rep 6: 532-538, 2017.
APA
Lee, D., Law, P., Ln, W., Loh, H.H., Song, K.Y., & Choi, H.S. (2017). Differential regulation of mouse and human Mu opioid receptor gene depends on the single stranded DNA structure of its promoter and α-complex protein 1. Biomedical Reports, 6, 532-538. https://doi.org/10.3892/br.2017.877
MLA
Lee, D., Law, P., Ln, W., Loh, H. H., Song, K. Y., Choi, H. S."Differential regulation of mouse and human Mu opioid receptor gene depends on the single stranded DNA structure of its promoter and α-complex protein 1". Biomedical Reports 6.5 (2017): 532-538.
Chicago
Lee, D., Law, P., Ln, W., Loh, H. H., Song, K. Y., Choi, H. S."Differential regulation of mouse and human Mu opioid receptor gene depends on the single stranded DNA structure of its promoter and α-complex protein 1". Biomedical Reports 6, no. 5 (2017): 532-538. https://doi.org/10.3892/br.2017.877
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