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Transcriptional regulation of the human factor IX promoter by the orphan receptor superfamily factors, HNF4, ARP1 and COUP/Ear3
Author(s) -
Naka H.,
Brownlee G.G
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.269808.x
Subject(s) - transcription factor , hepatocyte nuclear factor 4 , neuron derived orphan receptor 1 , transactivation , orphan receptor , factor ix , biology , haemophilia b , binding site , microbiology and biotechnology , genetics , nuclear receptor , gene , haemophilia , haemophilia a
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 ⊥36 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 Yelements, 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.