FOXa2/HNF3b-, MafA-, and PAX6-dependent synthesis of Pdx1 protein

Stable Identifier
R-MMU-186507
Type
Reaction [omitted]
Species
Mus musculus
Compartment
General
SVG |   | PPTX  | SBGN
FOXa2/HNF3b-, MafA-, and PAX6-dependent synthesis of Pdx1 protein

Binding of FOXa2/HNF3-beta to the 5'-flanking regions of the human, mouse and rat Pdx1 gene has been observed in vitro and in transient transfection studies (Sharma et al. 1997; Wu et al, 1997; Marshak et al. 2000; Gerrish et al. 2000; Ben-Shushan et al. 2001). Specifically, Foxa2 binding to the mouse Pdx1 distant enhancer region was shown in pancreatic beta-cells by ChIP analysis (Samaras et al. 2002). Moreover, the distant 5' flanking region of the Pdx1 gene containing a high-affinity binding site for FOXa2 is sufficient to drive beta-cell specific expression in transgenic mice (Samaras et al. 2002), and beta-cell specific ablation of Foxa2 results in down-regulation of Pdx1 mRNA and protein levels (Lee et al. 2002).

In vitro binding of MafA to a conserved 5'-flanking region of the Pdx1 and transactivation of this gene were observed in cultured beta-cell lines (Samaras et al. 2003). Deletion of MafA in mice causes decreased Pdx1 expression (Zhang et al, 2005).

Mutational analysis of the same 5'-flanking region that MafA binds on the Pdx1 gene in cultured beta-cells, indicates that PAX6 binds and transactivates Pdx1 (Samaras et al. 2002).

Literature References
PubMed ID Title Journal Year
12145169 Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo

Lee, CS, Sund, NJ, Vatamaniuk, MZ, Matschinsky, FM, Stoffers, DA, Kaestner, KH

Diabetes 2002
12052878 Conserved sequences in a tissue-specific regulatory region of the pdx-1 gene mediate transcription in Pancreatic beta cells: role for hepatocyte nuclear factor 3 beta and Pax6

Samaras, SE, Cissell, MA, Gerrish, K, Wright, CV, Gannon, M, Stein, R

Mol Cell Biol 2002
15923615 MafA is a key regulator of glucose-stimulated insulin secretion

Zhang, C, Moriguchi, T, Kajihara, M, Esaki, R, Harada, A, Shimohata, H, Oishi, H, Hamada, M, Morito, N, Hasegawa, K, Kudo, T, Engel, JD, Yamamoto, M, Takahashi, S

Mol Cell Biol 2005
12551916 The islet beta cell-enriched RIPE3b1/Maf transcription factor regulates pdx-1 expression

Samaras, SE, Zhao, L, Means, A, Henderson, E, Matsuoka, TA, Stein, R

J Biol Chem 2003
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