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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Zinc finger protein ZBTB20 is a key repressor of alpha-fetoprotein gene transcription in liver
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Zinc finger protein ZBTB20 is a key repressor of alpha-fetoprotein gene transcription in liver

机译：锌指蛋白ZBTB20是肝脏中甲胎蛋白基因转录的关键阻遏物

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The alpha-fetoprotein (AFP) gene is highly activated in fetal liver but is dramatically repressed shortly after birth. The mechanisms that underlie AFP transcriptional repression in postpartum liver are not well understood. AFP enhancer, repressor region, and promoter are implicated to be involved in AFP postnatal repression, but the major transcriptional repressor remains undefined. We previously identified a zinc finger protein gene Z6TB20. To determine its physiological functions in vivo, we have generated hepatocyte-specific ZBTB20 knockout mice by the Cre/loxP approach and demonstrated here that ZBTB20 ablation in liver led to dramatic derepression of the AFP gene in entire liver throughout adult life, although the hepatocytes were normally under nonproliferating status. Furthermore, we found that ZBTB20 was a transcriptional repressor capable of specifically inhibiting AFP promoter-driven transcriptional activity. Liver chromatin immuno-precipitation and mobility shift assays showed that ZBTB20 bound to AFP promoter directly. ZBTB20 was developmentally activated in liver after birth and inversely correlated with its AFP gene expression, suggesting that activated ZBTB20 expression in liver mediated AFP gene repression. Our data point to ZBTB20 as a key regulator governing AFP gene transcription and postulate a new model for the postnatal gene repression of AFP in liver.
机译：甲胎蛋白（AFP）基因在胎儿肝脏中被高度激活，但在出生后不久被显着抑制。产后肝脏中AFP转录阻抑的基础机制尚不清楚。暗示AFP增强子，阻遏物区域和启动子参与AFP出生后的阻遏，但主要的转录阻遏物仍然不确定。我们先前鉴定了锌指蛋白基因Z6TB20。为了确定其在体内的生理功能，我们通过Cre / loxP方法生成了肝细胞特异性ZBTB20基因敲除小鼠，并在这里证明了肝中的ZBTB20消融导致整个成年期整个肝脏中AFP基因的显着抑制，尽管肝细胞是通常处于不扩散状态。此外，我们发现ZBTB20是一个能够特异性抑制AFP启动子驱动的转录活性的转录阻遏物。肝染色质免疫沉淀和迁移率迁移分析表明ZBTB20直接与AFP启动子结合。 ZBTB20在出生后在肝脏中被发育激活，并与其AFP基因表达呈负相关，这表明激活的ZBTB20在肝脏介导的AFP基因抑制中表达。我们的数据表明ZBTB20是控制AFP基因转录的关键调控因子，并提出了肝脏AFP产后基因抑制的新模型。

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