Flowchart: Preparation: Pax4








Text Box: Activin A 





Text Box: Pax4Diabetes Type 1







Text Box: E47/E12                                    



Biochim Biophys Acta. 2006 Feb 13; [Epub ahead of print]

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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]