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

Stable Identifier
R-MMU-186507
Type
Reaction [omitted]
Species
Mus musculus
Compartment
nucleoplasm, cytosol
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | 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
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

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

Mol Cell Biol 2002
12145169 Foxa2 controls Pdx1 gene expression in pancreatic beta-cells in vivo

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

Diabetes 2002
15923615 MafA is a key regulator of glucose-stimulated insulin secretion

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

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

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

J Biol Chem 2003
Participants
Output
This event is regulated
Negatively by
Regulator
Foxo1 [nucleoplasm] (Mus musculus)
Regulator
Foxo1 [nucleoplasm] (Mus musculus)
Regulator
Foxo1 [nucleoplasm] (Mus musculus)
Positively by
Regulator
Pax6 [nucleoplasm] (Mus musculus)
Regulator
MafA [nucleoplasm] (Mus musculus)
Regulator
Foxa2 [nucleoplasm] (Mus musculus)
Orthologous Events
FOXOA2-, MAFA-, and PAX6-dependent synthesis of PDX1 protein (Homo sapiens)
Authored
Tello-Ruiz, MK  (2008-05-24)
Ferrer, J  (2008-05-24)
Reviewed
Jensen, J  (2008-05-13)
Created
Tello-Ruiz, MK  (2006-08-14)
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