Ectopic expression of TCF7L2 inhibits gluconeogenesis at the transcription level.

<p>A) Schematic representation of G6Pase (right) and PEPCK promoters (left). IRE: Insulin response element, CRE: cAMP response element, TBE: TCF binding element. B) Chromatin immunoprecipitation assay showing occupancy of TCF7L2 or CRTC2/FoxO1 over G6Pase and PEPCK promoters under feeding and fasting conditions. Representative data from at least three independent experiments are shown. C) Q-PCR analysis showing effects of TCF7L2 wild type and mutants on expression levels of gluconeogenic genes in mouse primary hepatocytes (<i>n</i> = 3 for each group). ΔHMG: TCF7L2 containing mutations in DNA binding motif, Δβ-catenin: TCF7L2 containing mutations in the beta-catenin binding motif. Representative data from at least three independent experiments are shown. D) Chromatin immunoprecipitation assay showing effects of TCF7L2 wild type and mutants on CRTC2 or FoxO1 occupancy over G6Pase and PEPCK promoters in mouse primary hepatocytes. Occupancy of CRTC2 (top) or FoxO1 (bottom) over G6Pase and PEPCK promoters was shown. Data are shown as the relative enrichment of IP/input ratios of each antibody over that of IgG control. Representative data from at least three independent experiments are shown. Data in B–D) represent mean ± SD (*;<i>P</i><0.05, **;<i>P</i><0.005, ***;<i>P</i><0.0005, t-test).