A common liver‐specific factor binds to the rat albumin and α‐foetoprotein promoters in vitro and acts as a positive trans‐acting factor in vivo

Abstract

Rat liver nuclear extracts were tested for the presence of factors which might be common to the transcriptional regulation of both the albumin and .alpha.-foetoprotein genes. Gel shift assay showed the formation of three complexes (I, II and III) with the albumin probe. Two of them (I and III) could be displaced by the .alpha.-foetoprotein promoter. Analysis of nuclear extracts from liver, kidney, spleen and brain and competition experiments using several oligonucleotides covering regions from the albumin and .alpha.-foetoprotein promoters showed that complex III results from the binding of the ubiquitous nuclear factor 1, while complex II involves a CCAAT-box-binding protein also detected in brain and spleen extracts. Complex I is formed upon binding of a liver-specific factor to a proximal element of the rat albumin promoter. This factor also binds to a similar sequence in the .alpha.-foetoprotein promoter and is closely related to the hepatocyte nuclear factor 1, as shown by competition experiments using an oligonucleotide covering its target sequence on the .beta.-fibrinogen promoter. Transfection competition experiments indicated that, in vivo, this factor acts as a positive trans-acting element in the expression of both the rat albumin and .alpha.-foetoprotein genes.