Retinol-binding protein (RBP4) transports retinol in the circulation from hepatic stores to peripheral tissues.
Since little is known regarding the regulation of this gene,we analysed the cis-regulatory sequences
of the mouse RBP4 gene. Our data show that transcription of the gene is regulated through a bipartite
promoter: a proximal region necessary for basal expression and a distal segment responsible for cAMPinduction.
This latter region contains several binding sites for the structural HMGA1 proteins, which are
important to promoter regulation. We further demonstrate that HMGA1s play a key role in basal and
cAMP-induction of Rbp4 transcription and the RBP4 andHMGA1 genes are coordinately regulated in vitro
and in vivo.HMGA1acts to recruit transcription factors to the RBP4 promoter andwe specifically identified
p54nrb/NonO and protein-associated splicing factor (PSF) as components that interact with this complex.
Steroidogenic factor 1 (SF1) or the related liver receptor homologue 1 (LRH-1) are also associated with
this complex upon cAMP-induction. Depletion of SF1/LRH-1 by RNA interference resulted in a dramatic
loss of cAMP-induction.
Collectively, our results demonstrate that basal and cAMP-induced Rbp4 transcription is regulated by
a multiprotein complex that is similar to ones that modulate expression of genes of steroid hormone
biosynthesis. Since genes related to glucose metabolism are regulated in a similar fashion, this suggests
that Rbp4 expression may be regulated as part of a network of pathways relevant to the onset of type 2
diabetes.