Transcriptional regulation of mouse delta-opioid receptor gene. Role of Ikaros in the stimulated transcription of mouse delta-opioid receptor gene in activated T cells.
Delta-opioid receptors (DOR) present on T cells have been shown to mediate the immunomodulatory effects of endogenous and synthetic DOR agonists on T cells. Considerable evidence indicates that there is stimulated transcription of DOR gene in activated T cells, which is correlated with augmented expression of DOR and enhanced capacity of DOR agonists to affect the T-cell's functions. However, the molecular mechanism underlying the stimulated transcription of the DOR gene in activated T cells is still unclear. In the present study, we analyzed a 1.3-kb DNA fragment immediately upstream of the translation start site (-1300 to +1 bp, with the translation start site designated as +1) of the mouse DOR gene in EL-4 cells, a mouse lymphoma T cell line that exhibits enhanced expression of DOR transcripts when activated by phytohemagglutinin. Through both in vivo and in vitro experiments, we have demonstrated that increased binding activity of Ikaros at the Ikaros-binding site (-378 to -374) in the DOR promoter is required for the stimulated transcription of DOR gene in phytohemagglutinin-activated T cells.
Sun
Ping
P
Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA. sunx0078@tc.umn.edu
Loh
Horace H
HH
D000818:Animals; D001483:Base Sequence; D004247:DNA; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D051740:Ikaros Transcription Factor; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D017465:Receptors, Opioid, delta / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D010835:Phytohemagglutinins; D017465:Receptors, Opioid, delta; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor; D004247:DNA