NeuroD1- and Pdx1-dependent synthesis of glucokinase (Gck) protein

Stable Identifier
R-MMU-186510
Type
Reaction [omitted]
Species
Mus musculus
Compartment
General
SVG |   | PPTX  | SBGN
NeuroD1- and Pdx1-dependent synthesis of glucokinase (Gck) protein

NeuroD1 binds to control sequences of the mouse GK gene in vitro, and this binding is sensitive to mutagenesis in transient transfection analyses (Cissell et al. 2003; Moates et al. 2003). Moreover, NeuroD1 was shown to bind to the GK promoter in vivo by ChIP analysis and stimulate expression in pancreatic beta-cells (Moates et al. 2003).

Whether Pdx1 transactivates the glucokinase (GK) gene in vivo has been a controversial issue. Nevertheless, Pdx1 binds to control sequences of the human and mouse GK gene in vitro, and this binding is sensitive to mutagenesis in transient transfection analyses (Watada et al. 1996; Cissell et al. 2003). However, whereas Cissell et al. (2003) observed that Pdx1-specific antibodies against both the N and C termini of PDX1 selectively immunoprecipitate regulatory sequences of the GK gene, Chakrabarti et al. (2002) were unable to detect this association using a different Pdx1 antiserum. Disparity in results might be due to the different animal and cell line models used to study this regulation.

Literature References
PubMed ID Title Journal Year
11825903 Quantitative assessment of gene targeting in vitro and in vivo by the pancreatic transcription factor, Pdx1. Importance of chromatin structure in directing promoter binding.

Chakrabarti, SK, James, JC, Mirmira, RG

J Biol Chem 2002
12426319 Transcription factor occupancy of the insulin gene in vivo. Evidence for direct regulation by Nkx2.2.

Cissell, MA, Zhao, L, Sussel, L, Henderson, E, Stein, R

J Biol Chem 2003
12540614 BETA2 activates transcription from the upstream glucokinase gene promoter in islet beta-cells and gut endocrine cells

Moates, JM, Nanda, S, Cissell, MA, Tsai, MJ, Stein, R

Diabetes 2003
8866550 The human glucokinase gene beta-cell-type promoter: an essential role of insulin promoter factor 1/PDX-1 in its activation in HIT-T15 cells

Watada, H, Kajimoto, Y, Umayahara, Y, Matsuoka, T, Kaneto, H, Fujitani, Y, Kamada, T, Kawamori, R, Yamasaki, Y

Diabetes 1996
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