Synergic activation of the human Pregnancy-Specific Glycoprotein PSG-5 promoter by the gut-enriched Krüppel-like factor (GKLF/KLF4) and Sp1

BLANCHON, L.; NORES, R.; GALLOT, D.; MARCEAU, G.; YANG, V.; BOCCO, J.L.; LÉMERY, D.; GACHON, A-M.; DASTUGUE, B.; PANZETTA-DUTARI, G.; SAPIN, V.

Mainz

Conferencia; 9th Meeting of the International Federation of Placenta Associations (IFPA) and 10th Meeting of the European Placenta Group (EPG); 2003

International Federation of Placenta Associations (IFPA) y European Placenta Group (EPG)

OBJECTIVES: Pregnancy-Specific Glycoproteins (PSGs) are major placental proteins thought to be essential for the maintenance of gestation in mammalian species. However, little is known about the regulation of expression of the genes encoding these proteins during placentation. It was previously demonstrated that the transcription factor Krüppel-like factor 6 binds to highly conserved sequence within the PSG gene promoters including PSG-5. Informatics analysis revealed the presence of one potential binding site for another KLF family member, GKLF/KLF4, in the PSG-5 promoter, suggesting that the transcriptional regulation of PSG-5 may also dependant on GKLF. METHODS: Immuno-histological and Western-Blot experiments were used to define the placental co-localisation of PSG-5, Sp1 and GKLF. Gene promoter-reporter transfections and electrophoretic mobility-shift assays were realised using JEG-3 and Drosophila SL2 cell lines to check the regulation of PSG-5 by Sp1 and GKLF. RESULTS: We showed that GKLF is a transcriptional activator of the PSG5 gene and binds to –148/-133 (CPE-box) promoter sequence. Moreover, PSG5 promoter is synergically activated by GKLF and the Sp1 transcription factor which requires two different regions: the –148/-133 promoter sequence (CPE-box) for GKLF and the –443/-437 (GT-box) upstream element, for Sp1. CONCLUSION: For the first time, we demonstrated the molecular implications of KLF4 and Sp1 in placental physiology and gene regulation.