Fig. 4.

CRTC2 increases CREB occupancy over gluconeogenic genes. (A) Q-PCR analysis of gluconeogenic gene expression in wild-type or CRTC2^−/− primary hepatocytes under basal conditions and following exposure to glucagon (n = 3, P < 0.05; SEM). Effect of adenoviral CRTC2 or green fluorescent protein (GFP) expression shown. (B and C) ChIP assays of CRTC2 (B) and CREB (C) occupancy over G6Pase and PEPCK promoters in wild-type or CRTC2^−/− hepatocytes (n = 3, P < 0.05; SEM). Exposure to glucagon indicated. Effect of adenoviral CRTC2 expression relative to control (Ad-GFP) shown. (D) Model for activation of the gluconeogenic program by CREB and CRTC2 during fasting. Increases in circulating glucagon trigger CRTC2 dephosphorylation and nuclear entry. Binding of nuclear CRTC2 to CREB increases CREB binding to relevant promoters.