Activin A-induced expression of PAX4 in AR42J-B13 cells involves the increase in transactivation of E47/E12

Rei Kanno, Takeshi Ogihara, Yasuhiro Igarashi, Yasushi Tanaka, Stuart B. Smith, Itaru Kojima, Michael S. German, Ryuzo Kawamori, Hirotaka Watada

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Pax4 is a paired-homeodomain containing transcriptional factor that controls the differentiation of pancreatic β 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 ∼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)-1α. Mutation introduced in each binding site markedly reduced activin A responsiveness. It has been reported that HNF-1α 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.

Original languageEnglish
Pages (from-to)44-50
Number of pages7
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1759
Issue number1-2
DOIs
Publication statusPublished - 2006 Jan

Keywords

  • Gene regulation
  • Insulin
  • Pancreatic development
  • Pax4
  • Transcription factor
  • beta-cell

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Genetics

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