UGT1基因簇编码一类重要的Ⅱ相药物代谢酶（UDP-葡萄糖醛酸转移酶，UGT），由可变区和恒定区组成，任意一个可变外显子都可被选择性地剪接到下游的一套恒定外显子上，而形成多种UGT转录本。核受体（NR）是动物体内最丰富的转录因子家族之一，也是目前最成功的药物靶标之一，它们的配体几乎都能被UGT转化。申请者前期的研究发现很多NR成员显著共调控UGT1簇多个基因的转录，表明UGT与NR两大家族之间存在复杂的反馈调节网络，该网络对预测药物相互作用和预防人类疾病具有重要意义。申请者还在UGT1基因簇中发现了两个重要的增强子区可能介导NR对UGT1的共调控。本申请将采用染色质构象捕获技术考察这两个增强子区是否远程调控UGT1基因簇内多个基因的转录，并找出各调节性NR在这两个增强子区的顺式作用元件。该研究将进一步诠释人类UGT1基因多态性的生物学意义，并为临床合理用药提供理论依据。

The UGT1 gene cluster encodes an important family of phase II drug-metabolizing enzymes: UDP-glucuronosyltransferases (UGT). It is organized into variable and constant regions. Any variable exon can be alternatively spliced into a set of downstream common exons, producing variable UGT transcripts. Nuclear receptors (NR) are one of the most abundant families of transcription factors in metazoan，as well as one of the most successful drug targets. Their ligands can be almost conjugated by UGT. The applicant's previous work reveals that many NRs significantly co-regulated the transcription of a common set of UGT1 genes, demonstrating a complicated feedback regulatory network exists between UGT and NR families. This network has great implication for predicting drug-drug interaction and preventing human diseases. the applicant also found two important enhancers, which potentially mediate NR's co-regulation on UGT1 genes. In this application, chromosome conformation capture technology will be used to check whether these two enhances distally regulate transcription of multiple UGT1 genes. And further work will be done to identify the NR cis-acting elements within each functional enhancer. This work may help to further uncover the biological implications of UGT1 gene polymorphisms, and provide scientific foundations for reasonable clinical description.