Fig. 3.

AhR transactivates 1C cycle genes and increases hepatic PC levels. a Potential binding sites for transcription factors within SHP peak regions at 1C genes were identified using the JASPAR database, and the abundance of representative factor binding sites is shown (left). An AhR/Arnt binding motif is shown (right). b Mice (n = 5 mice per group) were fasted overnight (Fs) or fasted and refed for 6 h (Fd), and AhR occupancy within the SHP binding peak regions at the 1C genes was determined by liver ChIP assays. c Hepa1c1c7 cells were transfected with a Pemt-luc or Gnmt-luc construct containing the WT or mutated AhR binding site in the Pemt promoter along with expression plasmids as indicated and treated with FGF19 for 2 h, and luciferase activity was measured (n = 5). d–g AhR transgenic mouse studies: Liver tissues were collected from WT littermate and CA-AhR transgenic mice (n = 4–7 mice per group), or C57BL/6 (WT control) and AhR-KO mice (n = 5–10 mice per group) and d, e mRNA levels of selected 1C genes and f, g 1C cycle metabolites were measured by qRT-PCR and LC–MS analysis, respectively. Means ± SD are shown, and statistical significance was measured using d–g Student’s t-test or b, c two-way ANOVA with the FDR post-test. *P < 0.05, **P < 0.01, NS, not statistically significant