氮排放问题制约我国养猪业可持续发展。氨在猪肝脏门静脉周肝细胞代谢为尿素，而在肝静脉周肝细胞合成谷氨酰胺等氨基酸。氨代谢差异受Wnt∕β-catenin通路调控，课题组发现猪肝脏Wnt∕β-catenin通路受组蛋白乙酰化酶修饰。那么调控猪肝细胞氨代谢差异的乙酰化酶是什么？是由于组蛋白乙酰化酶对β-catenin的乙酰化位点不同，还是组蛋白乙酰化差异引起了Wnt∕β-catenin通路被招募到不同的DNA区域调控基因表达，导致了门静脉周和肝静脉周肝细胞的氨代谢差异？本研究拟在已建立的门静脉周、肝静脉周肝细胞分离与培养基础上，研究肝细胞氨代谢差异及组蛋白乙酰化特点；采用TAP/MS等技术研究组蛋白乙酰化酶对β-catenin乙酰化特点；采用ChIP技术，分析Wnt∕β-catenin通路关键蛋白DNA结合区域组蛋白乙酰化差异规律。通过表观遗传学和分子营养学结合，旨在揭示猪肝脏氨代谢的差异机理。

Nitrogen emissions have become a grave social concern, which seriously restricts the sustainable development of China's pig industry. In contrast to conversion of ammonia into glutamine and other amino acids in perivenous hepatocytes, ammonia in periportal hepatocytes is responsible for urea synthesis. With regard to the difference of hepatic ammonia metabolism, it has been demonstrated that the distinct metabolic patterns are determined (influenced) by Wnt∕β-catenin pathway. According to our further endeavor, hepatic Wnt∕β-catenin pathway was modified by histone acetylation. Given this research background, we are wondering what is the key histone acetylase regulating the different ammonia metabolism in periportal and perivenous hepatocytes. Moreover, what is the sophisticated mechanism involved, discrepancy in gene expression as a result of binding between Wnt/β-catenin pathway to different region of DNA due to different histone acetylation, or different acetylated sites of β-catenin by histone acetylase? This program is based on the periportal and perivenous hepatocytes isolation and culture system, both of which were successfully established to explore the differences of ammonia metabolism and histone acetylation characteristics. TAP/MS techniques are used to investigate the acetylation characteristics of β-catenin by histone acetylase. On the other hand, the histone acetylation regular pattern of key protein DNA binding domain in the Wnt/β-catenin pathway is analyzed by ChIP techniques. By the combination of epigenetic and molecular nutrition, we finally attempt to reveal the mechanism of hepatic ammonia metabolism in pigs.