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- Title
STAT6 transcription factor binding sites with mismatches within the canonical 5′-TTC…GAA-3′ motif involved in regulation ofδ- andµ-opioid receptors.
- Authors
Börner, Christine; Wöltje, Michael; Höllt, Volker; Kraus, Jürgen
- Abstract
Opioid receptors are expressed in neuronal and immune cells and regulated in response to immunological processes. Herein, we demonstrate up-regulation of theδ-opioid receptor gene by interleukin-4 in immune cells (primary T and polymorphonuclear leukocytes, Jurkat E6 T cells), and in NG 108–15 neuronal cells. We identified an interleukin-4-responsive element at nt−671 on the murine gene promoter, to which the transcription factor STAT6 binds, as shown by reporter gene analysis and STAT6/DNA interaction studies in living cells with transcription factor decoy oligonucleotides. STAT6 normally binds to palindromic DNA motifs with a 5′-TTC...GAA-3′ core. Notably, theδ-opioid receptor STAT6 site (5′-TTC...GA-3′) is an imperfect palindrome with a mismatch within this core sequence. A systematic analysis of possible mismatch 5′-TTC...GAA-3′ motifs revealed that STAT6 also binds to the sequence 5′-TT...GAA-3′. This motif occurs as a polymorphism in the humanµ-opioid receptor gene (J. Biol. Chem 276, 43901–43908). We show that this mutated element has a significantly reduced STAT6 binding activity which correlates to its reduced interleukin (IL)-4 inducibility. In contrast, the non-canonical STAT6 site of theδ-opioid receptor binds STAT6 with similar high activity as a perfectly palindromic STAT6 site and is strongly inducible by IL-4.
- Subjects
OPIOID receptors; DRUG receptors; BINDING sites; CELL membranes; INTERLEUKIN-4; TRANSCRIPTION factors; NEUROCHEMISTRY; NEUROSCIENCES
- Publication
Journal of Neurochemistry, 2004, Vol 91, Issue 6, p1493
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2004.02846.x