甲基化是核酸和蛋白质的一种重要的修饰方式，具有调控基因表达、调节蛋白质功能以及影响核糖核酸（RNA）加工等作用，与癌症、衰老、老年痴呆等许多疾病密切相关，是表观遗传学的重要研究内容之一。虽然不断有新的甲基化过程被发现，但各种甲基化过程的调控机理仍然不是十分清楚，主要原因在于缺乏相应蛋白/DNA复合体的结构动力学信息。核磁共振波谱学在蛋白质的溶液三维结构测定和弱相互作用研究方面独具特色，基于甲基的NMR检测技术被认为是研究蛋白质构象变化特别是大分子量蛋白质复合体相互作用的重要工具，但此类方法易受背景信号影响，需要复杂同位素标记，并结合适当的滤波技术才能实现。本项目拟以组蛋白、DNA等甲基化相关蛋白质复合体系为对象，开展蛋白质结构动力学新技术和新方法研究，建立无需选择性标记的生物分子甲基化动力学NMR测定技术，在原子水平上研究接近生理条件下甲基化生物大分子相互作用的机制。

DNA or protein methylation is a critical epigenetic modification involved in gene expression, protein function regulation and RNA processing, playing an important role in the development of diseases such as cancer and Alzheimer's disease. Nowadays, more and more new patterns about biomolecule methylation have been found, however, the mechanism of methylation is still unclear, because the lack of three dimensional structure and dynamics information of methylated DNA or protein complex. Methyl specific analysis by NMR spectroscopy has been widely used to provide atomic-level resolution structural and dynamical information for biomolecule complex. However, they are difficult to be achieved due to complicated Isotope labeling, and serious impact of background signals. To solve the solution structure of and dynamics of the complex consisting of methylated protein or DNA and its ligand molecules, the project will: develop new NMR approaches to selectively detect methyl groups of methylated proteins and DNA; solve the structure and dynamics of the molecule complex in physiological conditions without specific isotopic labelling; explore the formation mechanism of those complex methylated histone and DNA involved.