Abstract
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.
Original language | English |
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Pages (from-to) | 3439-3447 |
Number of pages | 9 |
Journal | Frontiers in Bioscience |
Volume | 13 |
Issue number | 9 |
DOIs | |
State | Published - 2008 |
Keywords
- Gene regulation
- Presenilin 1
- Transcription
- Transcription factors
- Zinc finger protein