Transcriptional regulation of mouse delta-opioid receptor gene. Ikaros-2 and upstream stimulatory factor synergize in trans-activating mouse delta-opioid receptor gene in T cells.
Considerable evidence indicates that transcription of the delta-opioid receptor (dor) gene is correlated with both the expression of DOR on T cells and the capacity of DOR agonists to modulate the immunological functions of the T cell. We previously reported that increased Ikaros (Ik) binding activity over an Ik-binding site at -378 to -374 (with the translation start site designated as +1) in the mouse dor promoter was required for the enhanced transcription of dor gene in phytohemagglutinin-activated EL-4 cells, a mouse T cell line that constitutively expresses DOR. In the present study, we have analyzed further the mouse dor promoter in EL-4 cells and have demonstrated that Ik-2 homodimers bind to the -378/-374 Ik-binding site and exerts a position-dependent trans-activation effect on the dor promoter. Moreover, an E box (-185 to -180) that binds upstream stimulatory factor is essential for the dor promoter activity in both resting and phytohemagglutinin-activated T cells. Furthermore, we have demonstrated that Ik-2 and upstream stimulatory factor synergize in trans-activating the dor promoter via the putative Ik-binding site and the E box, respectively.
Sun
Ping
P
Department of Pharmacology, University of Minnesota Medical School, Minneapolis 55455, USA. sunx0078@tc.umn.edu
Loh
Horace H
HH
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D004268:DNA-Binding Proteins; D019281:Dimerization; D005786:Gene Expression Regulation; D051740:Ikaros Transcription Factor; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017465:Receptors, Opioid, delta / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D017465:Receptors, Opioid, delta; D011994:Recombinant Proteins; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor; D008156:Luciferases