title: Regulation of the alpha-fetoprotein promoter: Ku binding and DNA spatial conformation.
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.
authors.affiliation: Laboratoire 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.
authors.forename: P
authors.initials: P
authors.lastname: Liénard
authors.forename: C
authors.initials: C
authors.lastname: De Mees
authors.forename: P-L
authors.initials: PL
authors.lastname: Drèze
authors.forename: M
authors.initials: M
authors.lastname: Dieu
authors.forename: J-F
authors.initials: JF
authors.lastname: Dierick
authors.forename: M
authors.initials: M
authors.lastname: Raes
authors.forename: J
authors.initials: J
authors.lastname: Szpirer
authors.forename: C
authors.initials: C
authors.lastname: Szpirer
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D051537:Hepatocyte Nuclear Factor 1; D006801:Humans; D000072200:Ku Autoantigen; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D051381:Rats; D000509:alpha-Fetoproteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D000509:alpha-Fetoproteins; D051537:Hepatocyte Nuclear Factor 1; D004247:DNA; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; C000606511:Xrcc6 protein, rat; D000072200:Ku Autoantigen