H. Naka et Gg. Brownlee, TRANSCRIPTIONAL REGULATION OF THE HUMAN FACTOR-IX PROMOTER BY THE ORPHAN RECEPTOR SUPERFAMILY FACTORS, HNF4, ARP1 AND COUP EAR3/, British Journal of Haematology, 92(1), 1996, pp. 231-240
A study of the human clotting factor IX promoter by DNase I footprinti
ng 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 (nucleo
tides -15 to +3) and Y (nucleotides +15 to +36),in addition to the wel
l-known element centred around nucleotide -20. Other members of the or
phan 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 i
n 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 f
actor expression in these patients, but is unlikely to be the only fac
tor involved.