Analysis of cohesin model in CYP3A4 gene and individual phenotypic status

我们发现，细胞色素P3A4增强子区域的DNA甲基化是决定个体肝脏细胞色素P3A4基因表达水平的关键因素。染色体构象捕获(3C)分析表明增强子区域和转录起始点之间存在长距离顺式相互作用。众所周知，miR-122在人肝脏中有特异性表达，去唾液酸糖蛋白受体(ASGP-R)是一种肝脏特异性蛋白。我们建立了用抗ASGP-R多克隆抗体免疫沉淀的方法，从外周血中分离出表达miR-122的外周血细胞。这些结果表明，分离的细胞来自人肝细胞。所建立的方法可用于检测外周血中人肝DNA甲基化状态。

We showed that DNA methylation in CYP3A4 enhancer region is critically involved in determining the individual hepatic CYP3A4 mRNA level. Chromosome Conformation Capture (3C) assay suggested long-range cis-interaction between the enhancer region and the transcription start site. It is well known that miR-122 shows specific expression in human liver and asialoglycoprotein receptor (ASGP-R) is a liver-specific protein. We established the method using immuno-precipitation with polyclonal antibody against ASGP-R, to isolate the circulating cells showing miR-122 expression from peripheral blood. These results suggest that the isolated cells is from human liver cells. The established method can be used for the detection of human liver DNA methylation status using peripheral blood.