CLONING AND CHARACTERIZATION OF THE 5'-FLANKING REGION OF THE HUMAN DOPAMINE D4 RECEPTOR GENE

Dopamine D4 receptor (DRD4) has received attention in terms of pathoge nesis of schizophrenia and association with human personalities, We is olated the human DRD4 gene containing the 5'-flanking region and deter mined its sequence. Analysis of the DRD4 transcripts by 5'-RACE (5'-ra pid amplification of cDNA ends) revealed a region of the transcription initiation located between -501 and -436 relative to the first nucleo tide of the initiation codon, There is a CPG island spanning from -900 to + 500 but no TATA or CAAT boxes in the 5'-flanking region. Functio nal analysis of the 5'-flanking region of the DRD4 gene by a transient expression method revealed the presence of a negative modulator betwe en -770 and -679. The region between -591 and -123 gave the highest tr anscriptional activity in IMR32 (neuroblastoma) and Y-79 (retinoblasto ma) cells but not in HeLa cells, suggesting that this housekeeping gen e-like promoter regulates the cell-type specific gene expression. (C) 1997 Academic Press.