Diabetes Type 1
Activin A-induced expression of PAX4 in AR42J-B13 cells
involves the increase in transactivation of
E47/E12.
Kanno R, Ogihara T, Igarashi
Y, Tanaka
Y, Smith
SB, Kojima
I, German
MS, Kawamori R, Watada H.
Department of Medicine, Metabolism and Endocrinology, Juntendo
University School of Medicine, 2-1-1
Hongo, Bunkyo-ku, Tokyo
113-8421, Japan.
Pax4 is a paired-homeodomain containing
transcriptional factor that controls the differentiation of pancreatic beta
cells. The aim of this study was to investigate the mechanism of PAX4
expression by activin A. By reporter gene analysis
using AR42J-B13 cells, in which treatment with activin
A induced PAX4 mRNA expression, we identified that
a short sequence located approximately 1930 bp
upstream of the transcriptional start site is essential for activin A induced PAX4 promoter activation. This region
contains an E box and binding sites for hepatocyte
nuclear factor (HNF)-1alpha. Mutation introduced in each binding site
markedly reduced activin A
responsiveness. It has been reported that HNF-1alpha synergizes with basic
helix-loop-helix (bHLH) proteins in activating
the PAX4 promoter, and we demonstrated that activin
A strongly enhanced the functional activity of E47/E12 without the increase
in its binding ability. In addition, suppression of E47/E12 expression in
AR42J-B13 cells using siRNA oligonucleotides
results in the significant decrease in the intrinsic activin
A-induced PAX4 expression. Our results suggest that activin
A enhances PAX4 expression by enhanced transactivation
of E47/E12 proteins and might result in a cumulative transactivation
of the promoter.
PMID: 16546275 [PubMed - as supplied by
publisher]
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