ADR1 interacts with a down-stream positive element to activate PS1 transcription

We have identified downstream promoter sequence of the PS1 gene that may be regulated by novel transcription factors. 3′ deletion from +178 to +165 had no effect on PS1 transcription. 3′ deletion from +178 to +140 decreased promoter activity by 50%. Further 3′ deletion from +178 to +114 decreased promoter activity by 80%. Therefore, a crucial element controlling over 80% of the promoter activity in SK-N-SH cell line is located between +114 and +165. Electrophoretic mobility shift assays suggested that zinc finger proteins Sp1 and ADR1 interacted with the PS1 promoter sequence (+114 to +140) and promoter region (+140 to +165) respectively. A three base pair substitution within the core sequence (GGCGGGGA to GGCGactA) of the ADR1 consensus in the element (+140 to +165) that abolished ADR1-DNA interaction, reduced PS1 transcription by 50%. The substitution mutation in the sequence (+114 to +140) that abolished Sp1-DNA interaction had no effect on PS1 expression. These data suggest that a novel mammalian trans-activator protein ADR1 binds to the downstream element (+140 to +165) to activate PS1 transcription.