title: Transcriptional regulation of the human factor IX promoter by the orphan receptor superfamily factor, HNF4, ARP1 and COUP/Ear3.
abstract: A study of the human clotting factor IX promoter by DNase I footprinting and gel shifts in vitro, and by functional analysis of HepG2 cells in vivo, suggests that the liver-enriched transcription factor, HNF4, is involved in transactivating two cis-acting elements, i.e. X (nucleotides -15 to +3) and Y (nucleotides +15 to +36), in addition to the well-known element centred around nucleotide -20. Other members of the orphan receptor superfamily, e.g. ARP1 and COUP/Ear3, repress the factor IX promoter possibly by competition with HNF4 binding sites in the X and Y elements, but probably not at the -20 element. Mutations at -6 in the promoter, similar to those found in patients with haemophilia B, hinder HNF4 binding and transactivation of the X element, suggesting that impaired HNF4 binding contributes to the down-regulation of the factor IX expression in these patients, but is unlikely to be the only factor involved.
authors.affiliation: Chemical Pathology Unit, Sir William Dunn School of Pathology, University of Oxford.
authors.forename: H
authors.initials: H
authors.lastname: Naka
authors.forename: G G
authors.initials: GG
authors.lastname: Brownlee
mesh_terms: D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051838:COUP Transcription Factor I; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D018929:Cell Culture Techniques; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005164:Factor IX / Q000235:genetics*; D005786:Gene Expression Regulation; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011987:Receptors, Steroid; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051838:COUP Transcription Factor I; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; D005164:Factor IX; D051557:Hepatocyte Nuclear Factor 4; D010750:Phosphoproteins; D011987:Receptors, Steroid; D014157:Transcription Factors; C403128:MLX protein, human; C497589:NR2F1 protein, human; C095569:NR2F2 protein, human