睾丸特有的核小体变体及其调控因子的结构与动力学研究

我们将研究精子形成过程中，睾丸中特有的组蛋白变体组装的核小体；组蛋白的分子伴侣；染色质重塑蛋白质因子的结构，动力学。回答以下科学问题：.1、睾丸中特有的组蛋白变体组装进核小体，如何影响核小体的结构及稳定性？其动力学特征是什么？2、与精子形成过程相关的组蛋白分子伴侣的结构，它们与核小体如何相互作用，行使功能？3、睾丸中特有的与组蛋白乙酰化相关的染色质重塑蛋白因子的结构，它们与核小体如何相互作用，行使功能？通过研究，力图将表观遗传调控的结构生物学研究由研究蛋白质-多肽相互作用，推向研究蛋白质与核小体作用；将核磁共振研究由小蛋白质推向超大分子；方法技术有所创新。我们实验室在表观调控的结构生物学研究方面具有相当基础。在Genes & Developmen, JBC, J. strut.Bio. 等学术期刊发表一批论文，文章被许多重要综述期刊引用。

During spermatogenesis, postmeiotic male germ cells undergo extensive chromatin remodeling. This process involves large-scale incorporation of testis specific histone variants, creating less stable nucleosomes; genome-wide histone hyperacetylation; and the testis specific chromatin remodeling protein factors function. That causes chromatin more open in certain areas. We will study the testis-specific histone variants, histone chaperone and chromatin remodeling protein factor by structural biology methods to answer following questions:.1..The testis-specific histone variants substituted in the nucleosome, how to influence nucleosome structure and stability? What are its dynamic properties?.2. Histone chaperone related with spermatogenesis, how they interact with the nucleosome. How they perform their function?.3. The structure of testis-specific chromatin remodeling protein factor that related with histone acetylaion, how they interact with the nucleosome. How they perform their function?.Our research will promote the structural biology research of epigenetic regulation from studying interaction between protein and peptide to the level interaction between protein and nucleosome. It also will promote the NMR studying from small proteins (MW <20 kDa ) to supermolecules. During the investigation, we will also concerning methodology development.. In the structural biology investigation for epigenetic regulation, our laboratory already has solid background. We have published series papers in international Journal such as Genes & Developmen, JBC, J. strut.Bio., et al. Papers were cited by many important journal that publish review articles.