高等真核生物和人的细胞中,DNA甲基化（5-甲基胞嘧啶）是重要的染色质修饰之一,其主要功能是抑制基因表达.大多数DNA甲基化发生在胞嘧啶-鸟嘌呤(CpG)序列中. 在真核生物中, CpG 岛位于基因启动子附近,该区域富含CpG, 且其中的CpG保持非甲基化状态，CpG岛对于基因转录的调控一直以来都是表观遗传调控的热点。已知CXXC锌指结构域是CpG双链DNA的阅读器，人体内共有12个含CXXC结构域的蛋白质，这些蛋白质都是表观遗传中重要的效应分子。我们将利用结构生物学对CXXC家族进行系统性的结构功能研究，揭示CXXC、CXXC-PHD等模块识别CpG双链DNA的序列特异性，以及这种特异性背后的分子机制。在此基础上,我们希望利用细胞生物学、生物信息学等手段确定这些蛋白质基因组DNA中的定位，了解这些结合非修饰CpG的蛋白质，包括含CXXC结构域的蛋白质或蛋白质复合物，通过结合CpG后调控靶基因表达的机理。

In higher eukaryotic cells, such as human cells, DNA methylation exists as one of the important chromatin modifications and it plays an important role in gene repression. Most of DNA methylation occurs in the context of CpG in vivo. In eukaryotes, CpG islands are rich of CpG dinucleotides and those CpGs are maintained in unmodified status. CpG islands are usually near the transcription start sites of key genes, so how CpG islands affect eukaryotic gene expression is a hot topic in epigenetic gene regulation. It has been reported that CXXC Zinc finger domain serves as the reader of CpG double stranded DNAs (dsDNAs). There are 12 CXXC domain-containing proteins in human and all of them are important effectors in epigentics. We sought to utilize structural biology to investigate the CXXC domain family systematically to uncover the molecular mechanisms underling the CpG specific recognition by CXXC and CXXC-PHD modules. Furthermore, we plan to examine the localization of CXXC domain proteins or protein complexes in genomic DNA, and to understand how unmodified CpG binders, including CXXC domain containing proteins and complexes, regulate the target gene expression by binding to CpGs.