ALPHA FETOPROTEIN ENHANCERS/LIVER SPECIFIC TRANSCRIPTION

肝脏执行许多不同的功能，产生许多 血清蛋白、代谢酶、急性期反应物，以及 在有机体中维持体内平衡的解毒酶。 这些不同的功能需要协调调节许多 肝脏内的基因，许多基因必须表达，以应对 发育、激素和环境信号。 因此，肝脏 为研究基因调控机制提供了理想的器官。 该提案将研究小鼠α- 甲胎蛋白（AFP）基因增强子区。 AFP是主要的血清 在哺乳动物胎儿的蛋白质，AFP的确切功能是不是 知道的 它可能参与了胎儿的结合和运输 激素胆红素和有机阳离子 法新社也可以作为一个 免疫抑制剂，保护发育中的胎儿免受排斥， 母体免疫系统 尽管我们的免疫抑制剂可以保护 发育中的胎儿免受母体免疫系统的排斥。 尽管我们对AFP的功能缺乏了解， 提供了一个很好的模型系统来研究发展和 肝脏特异性转录控制。 该提案将解决 几个基本问题。 肝的分子基础是什么- 限制增强子活性？ 区域控制的基础是什么？ 成人肝脏中的基因表达 什么反式转录 因子参与基因表达的重编程， 肝再生 肝脏疾病，许多是由于不充分或不适当的 肝脏疾病期间的基因表达是一个主要的健康问题。 这些实验应该进一步阐明我们对 在正常和病理条件下在肝脏中的转录。 此外，从这些研究中获得的信息可能会改善 在肝脏内表达外源基因的策略，许多人的目标 基因治疗试验

The liver performs a number of different functions, producing many of the serum proteins, metabolic enzymes, acute-phase reactants, and detoxifying enzymes that serve to maintain homeostasis in an organism. These diverse functions require the coordinate regulation of numerous genes within the liver, and many genes must be expressed in response to developmental, hormonal, and environmental signals. Thus, the liver provides an ideal organ to study mechanisms of gene regulation. This proposal will investigate the regulation of the mouse alpha- fetoprotein (AFP) gene enhancer region. While AFP is the major serum protein in the mammalian fetus, the precise function of AFP is not known. It may be involved in the binding and transport of fetal hormones, bilirubin, and organic cations. AFP may also act as an immunosuppressant that protects the developing fetus from rejection by the maternal immune system. Despite our immunosuppressant that protects the developing fetus from rejection by the maternal immune system. Despite our lack of understanding regarding AFP function, this gene provides an excellent model system to investigate developmental and liver-specific transcriptional control. This proposal will address several fundamental questions. What is the molecular basis of liver- restricted enhancer activity? What is the basis of zonal control of gene expression in the adult liver? What trans-acting transcription factors are involved in the reprogramming of gene expression during liver regeneration? Liver disorders, many which are due to insufficient or inappropriate gene expression during liver disease, represent a major health concern. These experiments should elucidate further our understanding of transcription in the liver during normal and pathological conditions. In addition, the information derived from these studies may improve strategies to express foreign genes within the liver, a goal of many gene therapy trials.