b-catenin signaling can be both a physiological and oncogenic pathway in the liver. It controls compartmentalized gene expression, allowing the liver to ensure its essential metabolic function. It is activated by mutations in 20%-40% of hepatocellular carcinomas (HCCs) with specific metabolic features. We decipher the molecular determinants of b-catenindependent zonal transcription using mice with b-catenin-activated or -inactivated hepatocytes, characterizing in vivo their chromatin occupancy by T-cell factor (Tcf )24 and b-catenin, transcriptome, and metabolome. We find that Tcf-4 DNA bindings depend on bcatenin. Tcf-4/b-catenin binds Wnt-responsive elements preferentially around b-catenininduced genes. In contrast, genes repressed by b-catenin bind Tcf-4 on hepatocyte nuclear factor 4 (Hnf-4)-responsive elements. b-Catenin, Tcf-4, and Hnf-4a interact, dictating bcatenin transcription, which is antagonistic to that elicited by Hnf-4a. Finally, we find the drug/bile metabolism pathway to be the one most heavily targeted by b-catenin, partly through xenobiotic nuclear receptors. Conclusions: b-catenin patterns the zonal liver together with Tcf-4, Hnf-4a, and xenobiotic nuclear receptors. This network represses lipid metabolism and exacerbates glutamine, drug, and bile metabolism, mirroring HCCs with b-catenin mutational activation. (HEPATOLOGY 2014;59:2344-2357 See Editorial on Page 2080 T he adult liver is a quiescent organ, fully compartmentalized to accomplish its crucial metabolic role. Its vasculature gives rise to two distinct hepatocyte populations: one located in the vicinity of the portal vein and the other around the central vein. 1 Pericentral (PC) hepatocyte metabolism is complementary to that of periportal (PP) hepatocytes in terms of energy, ammonia, and xenobiotic metabolism. This complementarity arises as a result of the production of distinct specialized proteins in the two zones. 1,2 It has been demonstrated that the Wnt/b-catenin pathway is the master transcriptional regulator of this zonal metabolism, and that control is rendered by a Wnt morphogenetic concentration gradient high in PC hepatocytes and decreasing toward PP hepatocytes. 3,4

International audienceThe anisotropy of the oxygen anionic conductivity was measured for two mixed ionic electronic conducting (MIEC) oxides with the 2D K2NiF4-type structure, i.e., Nd2NiO4+δ and Pr2NiO4+δ, using high quality single crystals. Measurements of the oxygen diffusivity and surface exchange performed parallel and perpendicularly to the [001] direction, from 450 to 700 °C, using the isotope exchange depth profile (IEDP) technique, combining 16O/18O exchange and secondary ion mass spectroscopy (SIMS) are reported. For both materials the diffusion is about 3 orders of magnitude higher along the (a,b)-plane compared to the perpendicular (c-axis) direction. These values are among the highest when compared to several state-of-the-art MIEC materials. The diffusion along the (a,b)-plane for Pr2NiO4+δ is higher than that of Nd2NiO4+δ due to a much lower diffusion activation energy (0.5 and 1.4 eV for Pr2NiO4+δ and Nd2NiO4+δ, respectively). A large anisotropy is also observed in the surface exchange coefficient (k*) values for both materials, with (a,b)-plane coefficients being 1 to 1.5 orders of magnitude larger than those for the c-axis