Dopamine receptor regulating factor, DRRF: A zinc finger transcription factor

Dopamine receptor genes are under complex transcription control, determinin g their unique regional distribution in the brain. We describe here a zinc finger type transcription factor, designated dopamine receptor regulating f actor (DRRF), which binds to Gc and GT boxes in the D-1A and D-2 dopamine r eceptor promoters and effectively displaces Spl and sp3 from these sequence s. Consequently, DRRF can modulate the activity of these dopamine receptor promoters. Highest DRRF mRNA levels are found in brain with a specific regi onal distribution including olfactory bulb and tubercle, nucleus accumbens, striatum, hippocampus. amygdala, and frontal cortex. Many of these brain r egions also express abundant levels of various dopamine receptors. In vivo, DRRF itself can be regulated by manipulations of dopaminergic transmission . Mice treated with drugs that increase extracellular striatal dopamine lev els (cocaine), block dopamine receptors (haloperidol), or destroy dopamine terminals (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) show significant a lterations in DRRF mRNA. The latter observations provide a basis for dopami ne receptor regulation after these manipulations. We conclude that DRRF is important for modulating dopaminergic transmission in the brain.