长链非编码RNA(lncRNA)作为重要的表观调控因子在基因表达调控中发挥重要作用，但目前尚未见关于其调控药物代谢酶的研究。我们前期研究发现肝脏转录因子HNF1A相关lncRNA（lnc-HNF1A）的表达与HNF1A及肝脏代谢酶CYP3A4的表达均呈正相关，且CYP3A4的高表达与其基因启动子区组蛋白甲基化（H3K4me2）相关。由此假设：lnc-HNF1A作为HNF1A的辅激活因子参与CYP3A4表达调控。因此，本课题拟研究：1)采用过表达、RNA干扰明确lnc-HNF1A/HNF1A对CYP3A4表达的影响；2)研究lnc-HNF1A与HNF1A蛋白以及其他表观修饰酶的相互作用；3)探讨lnc-HNF1A/HNF1A通路对CYP3A4基因启动子区组蛋白修饰状态及染色质浓缩状态的影响。该课题从lncRNA调控的角度解释CYP3A4表达个体差异的分子机制，为临床个体化治疗提供新思路。

As part of the epigenetics, long non-coding RNAs (lncRNA) have been showed valuable roles in the regulation of gene expression. However, no study has revealed the effect of lncRNA on the regulation of drug metabolism enzymes. In preliminary studies, we have found that the expression of HNF1A related lncRNAs (lnc-HNF1A) were positively related with the expression of both HNF1A and CYP3A4. Besides, ChIP-seq data showed that the H3K4me2 level in CYP3A4 promoter was associated with the increase expression of CYP3A4. Based on these studies, we hypothesize that lnc-HNF1A may be a coactivator and interact with HNF1A to change the histone modifications and chromatin conformation in the promoter of CYP3A4 through recruiting histone methyltransferases and binding to specific sites in CYP3A4 promoter to activate the expression of CYP3A4. The aim of this study is to research the epigenetic mechanism in the regulation of CYP3A4 expression by identifying the role of lnc-HNF1A. Firstly, the effect of lnc-HNF1A on CYP3A4 expression in liver cells will be determined with gain-of-function and loss-of-function assays. Then, how lnc-HNF1A interacts with HNF1A and regulates the histone modifications will be studied. Finally, the changes of histone modifications and chromatin condensation of CYP3A4 promoter will be revealed. This study on lncRNA-controlled gene regulation shall not only improve mechanistic understanding of CYP3A4 individual variability but also provide novel insights into developing more effective therapeutic strategies.