IFITM基因是一族被干扰素诱导表达的基因，在抗多种病毒感染以及影响人群病毒易感性方面发挥着重要作用，因而研究其基因表达调控机制具有重要的意义。之前对IFITM基因表达调控研究主要集中在启动子区，但是在最近的研究中，我们发现增强子也参与到了IFITM基因的表达调控中。本项目拟利用增强子与靶基因启动子相互作用的理论基础，通过4C-seq获得干扰素处理前后IFTIM基因在全基因组的相互作用谱，并整合多组学数据，在全基因组范围内系统地鉴定IFITM基因的增强子；然后利用DNA pulldown、质谱、ChIP、CRISPR和RNAi等实验，从增强子上结合的调控性转录因子和介导启动子-增强子相互作用的蛋白两个方面，探究增强子调控IFITM基因的分子机制；最后以流感病毒感染为模型，分析IFITM基因的增强子在抗病毒感染中发挥的作用，以期为病毒易感性新位点的发现和抗病毒药物靶点的筛选提供新的思路。

IFITM genes are a family of interferon-induced genes, which play a vital role in defending multiple viruses and influencing virus susceptibility. Therefore, it is of great importance to study the regulatory mechanisms of IFITM gene expression. Previous research mainly focused on the promoters of IFITM genes, however, our recent study has indicated that enhancers are also involved in the expressional regulation of IFITMs. On the theoretical basis of enhancer physically interacting with promoters of target genes, this project will integrate genomewide interactome of IFTIM genes both before and after the treatment of interferons with multiple omic data, to systematically indentify enhancers of IFITM genes genomewide; then using DNA pulldown, mass spectrometry, ChIP, CRISPR and RNAi, we will investigate the molecular mechanism of newly indentified enhancers regulating IFITMs from two aspects: the regulatory transcription factors binding on the enhancers and the proteins that mediate the promoter-enhancer interactions; In the end, we will use the infection of influenza virus as the experimental model to study the biological significance of enhancers of IFITM genes in anti-virus process, thus providing new insights for finding new virus susceptibility loci and screening targets of anti-virus medicine.