The zfh-2 gene product is a potential regulator of neuron-specific dopa decarboxylase gene expression in Drosophila.
We have studied a 40-bp upstream regulatory region of the DOPA decarboxylase gene (Ddc) which is important for cell-specific expression in the Drosophila central nervous system (CNS). This region contains two redundant elements which when simultaneously mutated result in lowered DDC expression in serotonin neurons. We uncovered a protein binding site within one of these elements and have cloned a factor which binds to the site. This factor is the product of the zfh-2 gene, a complex homeodomain/zinc finger protein previously identified by binding to an opsin regulatory element. The in vivo profile of ZFH-2 in the larval CNS shows intriguing overlap with DDC in specific serotonin and dopamine neurons. We show that ZFH-2 is related to a human transcription factor ATBF1. The multiple homeodomain and zinc finger motifs in these two proteins show a similar linear arrangement which implies coordinate action among the motifs. In addition, the homology defines a new homeodomain subtype.
Lundell
M J
MJ
Department of Biology, University of Virginia, Charlottesville 22901.
Hirsh
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000235:genetics*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012701:Serotonin / Q000378:metabolism; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; C077729:Zfh2 protein, Drosophila; D012701:Serotonin; D004295:Dihydroxyphenylalanine; D004296:Dopa Decarboxylase