Regulation of the alpha-fetoprotein promoter: Ku binding and DNA spatial conformation.
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.
Liénard
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P
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.
De Mees
C
C
Drèze
P-L
PL
Dieu
M
M
Dierick
J-F
JF
Raes
M
M
Szpirer
J
J
Szpirer
C
C
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
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