高能低蛋白日粮诱导的蛋鸡脂肪肝出血综合征表观遗传机制研究

蛋鸡脂肪肝出血综合征（FLHS）是一种营养代谢病，主要特征为肝脏脂肪过度沉积，产蛋率显著下降，给蛋鸡养殖业造成严重的经济损失。FLHS发病原因涉及多方面，而营养因素是目前养禽业FLHS发病的主要原因。营养可以通过表观遗传修饰影响基因的表达；而组蛋白修饰是一种重要的表观遗传现象，研究表明H3K14ac及H3K9me3组蛋白修饰在营养代谢性疾病的发生发展中发挥重要作用。目前，未见有FLHS表观遗传学方面的研究报道。本研究拟以海兰蛋鸡为试验对象，采用高能低蛋白日粮人工诱发FLHS，运用染色质免疫共沉淀-测序（ChIP-seq）技术比较FLHS患鸡和健康蛋鸡肝脏组蛋白修饰及染色质结构的差异，分析H3K14ac及H3K9me3表观修饰涉及的代谢通路，从表观遗传水平揭示FLHS的发生、发展机制，为FLHS有效防治提供新的理论依据，为人类脂肪肝研究提供借鉴和参考。

Fatty liver hemorrhagic syndrome (FLHS) is an avian nutritional and metabolic disease, characterized by increased hepatic triacylglycerol content associated with liver hemorrhages, resulting in a dramatic decline in egg production and causes great economic losses in poultry industry. Many factors were implicated as contributors to occurrence of FLHS. Of which, nutritional factor is the major cause of FLHS, especially, high energy and low protein diet. The impact of nutrition as an environmental agent in regulating key gene expression patterns can lead to phenotypical alterations. Histone modification is an important epigenetic phenomenon. Many studies revealed that H3K14ac and H3K9me3 play a key role in the metabolic diseases. In this proposed study, Hanlan layer hens will be employed to create disease model of FLHS by feeding high energy/low protein diet. Subsequently, to investigate how H3K14ac and H3K9me3 regulated the expression of genes and involved in the molecular mechanism in FLHS, the changes of histone modifications and chromatin remodeling will be compared using Chromatin immunoprecipitation (ChIP) followed by sequencing. At the same time, a series of pathways which are related to carbohydrate metabolism, lipids metabolism and signal transduction will be analyzed according to the data of ChIP-seq in H3K14ac and H3K9me3, so as to elucidate the mechanisms of FLHS. These results will be benficial to understand the pathogenesis of FLHS and will provide basic research data and pave a new road for preventing FLHS.