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STAT6 transcription factor binding sites with mismatches within the canonical 5′‐TTC…GAA‐3′ motif involved in regulation of δ‐ and µ‐opioid receptors
Author(s) -
Börner Christine,
Wöltje Michael,
Höllt Volker,
Kraus Jürgen
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02846.x
Subject(s) - palindromic sequence , biology , stat6 , microbiology and biotechnology , transcription factor , receptor , reporter gene , gene , transcription (linguistics) , jurkat cells , chemistry , immune system , gene expression , palindrome , genetics , t cell , linguistics , philosophy , crispr
Opioid receptors are expressed in neuronal and immune cells and regulated in response to immunological processes. Herein, we demonstrate up‐regulation of the δ‐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, the δ‐opioid receptor STAT6 site (5′‐TTC…G G A‐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 A …GAA‐3′. This motif occurs as a polymorphism in the human µ‐opioid receptor gene (Kraus et al . 2001 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 the δ‐opioid receptor binds STAT6 with similar high activity as a perfectly palindromic STAT6 site and is strongly inducible by IL‐4.