WINGED HELIX HEPATOCYTE NUCLEAR FACTOR 3 AND POU-DOMAIN PROTEIN BRN-2N-OCT-3 BIND OVERLAPPING SITES ON THE NEURONAL PROMOTER OF HUMAN AROMATIC L-AMINO-ACID DECARBOXYLASE GENE/

The neuronal promoter of human aromatic L-amino acid decarboxylase gen e has been analysed to elucidate the mechanisms of neuron type-specifi c expression. The (- 560/ + 92) promoter segment was sufficient to dir ect luciferase expression at a higher level in SK-N-BE neuroblastoma c ells, than in CHP126 neuroepithelia, HepG2 hepatoma or SK-Hep1 epithel ioma cells. Deletions experiments showed that this segment contained a neuronal-specific (element T1) and a SK-N-BE-specific (element N1) ci s-activating sequences. Element T1 (- 72/ - 36) bound Spl and NF-Y pro teins, and unidentified neuronal-specific factors. Element N1 (- 102/ - 72) bound cell-specific factors, identified as HNF-3, N-Oct-3/Bm-2 a nd N-Oct-2. HNF-3 proteins recognized the sequence TCAGTAAATA that mat ches the consensus motif. Oct-1, N-Oct-2 and N-Oct-3 bound the AAATAAT GC sequence that overlaps the HNF-3 binding site. In addition, we show that the HNF-3 binding sites from aldolase C and HNF-3 beta gene prom oters also bind N-Oct-2 and N-Oct-3 proteins. These data suggest a fun ctional interplay of winged helix/forkhead and POU-domain transcriptio n factors on a variety of neuronal gene promoters. (C) 1998 Elsevier S cience B.V.