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Regulation of the alpha-fetoprotein promoter: Ku binding and DNA spatial conformation
P Liénard1, C De Mees, P-L Drèze
1Laboratoire de Biologie du Développement, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, 12, rue Professeurs-Jeener-et-amp-Brachet, 6041 Gosselies (Charleroi), Belgium.
Abstract:
This work shows that the proximal promoter of the mouse Afp gene contains a Ku binding site and that Ku binding is associated with down-regulation of the transcriptional activity of the Afp promoter. The Ku binding site is located in a segment able to adopt a peculiar structured form, probably a hairpin structure. Interestingly, the structured form eliminates the binding sites of the positive transcription factor HNF1. Furthermore, a DNAse hypersensitive site is detected in footprinting experiments done with extracts of AFP non-expressing hepatoma cells. These observations suggest that the structured form is stabilised by Ku and is associated with extinction of the gene in AFP non-expressing hepatic cells.
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