Dopamine receptor regulating factor, DRRF: a zinc finger transcription factor.
Dopamine receptor genes are under complex transcription control, determining their unique regional distribution in the brain. We describe here a zinc finger type transcription factor, designated dopamine receptor regulating factor (DRRF), which binds to GC and GT boxes in the D1A and D2 dopamine receptor promoters and effectively displaces Sp1 and Sp3 from these sequences. Consequently, DRRF can modulate the activity of these dopamine receptor promoters. Highest DRRF mRNA levels are found in brain with a specific regional distribution including olfactory bulb and tubercle, nucleus accumbens, striatum, hippocampus, amygdala, and frontal cortex. Many of these brain regions 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 levels (cocaine), block dopamine receptors (haloperidol), or destroy dopamine terminals (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) show significant alterations in DRRF mRNA. The latter observations provide a basis for dopamine receptor regulation after these manipulations. We conclude that DRRF is important for modulating dopaminergic transmission in the brain.
Hwang
C K
CK
Genetic Pharmacology Unit, Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA.
D'Souza
U M
UM
Eisch
A J
AJ
Yajima
S
S
Lammers
C H
CH
Yang
Y
Y
Lee
S H
SH
Kim
Y M
YM
Nestler
E J
EJ
Mouradian
M M
MM
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D003042:Cocaine / Q000494:pharmacology; D017124:Conserved Sequence; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011954:Receptors, Dopamine / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D018492:Dopamine Antagonists; C486609:Klf16 protein, mouse; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D014157:Transcription Factors; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003042:Cocaine; D006220:Haloperidol; D004298:Dopamine