Transcriptional auto-regulation of the dopamine receptor regulating factor (DRRF) gene

The murine dopamine receptor regulating factor (DRRF) gene is transcribed from a TATA-less promoter that has several putative Sp1 binding sites. The present investigation identifies functional transcription factors that modulate the expression of this gene. In the D2-dopamine receptor expressing NB41A3 cells, Sp1 potently activates transcription from the DRRF promoter in pCAT-DRRF-1153/+17, while DRRF itself effectively inhibits it. Sp1 also activates this promoter in pCAT-DRRF-310/+17. In competitive co-transfection experiments, DRRF represses the transcriptional activation induced by Sp1, while Sp1 de-represses the inhibitory effect of DRRF. Deletion of the 31 bp fragment between -1153 and -1122 decreased basal transcription down to about 60%. This fragment contains a functional AP1 binding site. In addition, deletion of the 129 bp region between -901 and -772 further decreased transcription. The latter region has a functional AP2 binding site. The present observations suggest that DRRF auto-regulates its own promoter by competing with Sp1 and that both AP1 and AP2 modulate expression of this gene.