正常情况下，甲胎蛋白（AFP）的表达具有严格的时空限制。出生后数周内，肝脏AFP的转录水平快速下降，仅维持于胎肝的万分之一左右，这其中的遗传信息学基础一直是未解之谜。锌指蛋白DPZF是我们自主发现并报道的新型转录抑制因子，其生物学功能尚不明确。我们利用基因打靶技术成功建立了DPZF基因敲除小鼠模型，发现DPZF基因缺陷小鼠出生后肝脏AFP基因表达一直维持在胎肝水平，并观察到DPZF体外过表达对AFP启动子活性具有明显抑制作用。本项目可望揭示AFP基因调控序列中参与其转录抑制的遗传信息学结构特征、新型转录因子DPZF对AFP转录调控的作用及其机理，剖析AFP基因表达的时空调控机理，并为深入认识DPZF基因缺陷小鼠的表型特征和DPZF转录调控机理打下基础，形成具有原始创新性的科研成果。

The alpha-fetoprotien (AFP) gene exhibits high tissue specificity and tight temporal regulation during the mammalian development. It is activated, together with the evolutionarily related albumin gene, in the yolk sac, fetal liver and fetal gut. Shortly after birth, it is rapidly repressed to extremely low but detectable levels in the liver and gut. Hence, AFP gene is regarded as an ideal model to investigate the developmental control of trnascription. Up to now, the mechanisms underlying the postnatal repression of AFP gene is poorly defined. We identified a novel POZ zinc finger protein DPZF, and generated the DPZF-deficient mice by homologous recombination. DPZF knockout mice exhibit consistently high expression of AFP in adult livers through their life, somehow close to the levels of this gene in fetal liver. Overexpression of DPZF in hepatoma cells dramatically inhibits AFP reporter activity. In this study, we will identify the cis-elements involved in the DPZF-mediated postnatal repression of AFP gene and the underlying mechanisms.

正常情况下，甲胎蛋白（AFP）的表达具有严格的时空限制。出生后数周内，肝脏AFP的转录水平快速下降，仅维持于胎肝的万分之一左右，这其中的遗传信息学基础一直是未解之谜。锌指蛋白DPZF是我们自主发现并报道的新型转录抑制因子，其生物学功能尚不明确。我们利用基因打靶技术成功建立了DPZF基因敲除小鼠模型，发现DPZF基因缺陷小鼠出生后肝脏AFP基因表达一直维持在胎肝水平，并观察到DPZF体外过表达对AFP启动子活性具有明显抑制作用。本项目可望揭示AFP基因调控序列中参与其转录抑制的遗传信息学结构特征、新型转录因子DPZF对AFP转录调控的作用及其机理，剖析AFP基因表达的时空调控机理，并为深入认识DPZF基因缺陷小鼠的表型特征和DPZF转录调控机理打下基础，形成具有原始创新性的科研成果。