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.