Paf1复合物(PAF1C)的装配机理及功能机制研究

Paf1复合物（PAF1C）是真核生物中非常保守的多功能复合物，协同调节多种组蛋白修饰和招募转录因子，进而调控基因表达。为了深入理解PAF1C中6个亚基装配的结构机理和功能机制，我们综合运用多学科交叉手段来研究PAF1C的装配机理及结构与功能关系。本项目将进行以下方面的研究：建立利用模式生物酵母来研究PAF1C体内功能机制的实验模型；Rtf1亚基识别组蛋白H2A/H2B底物的结构与功能；支架蛋白Ctr9亚基参与组装PAF1C的结构基础和调节机制；PAF1C与组蛋白修饰酶的相互作用。这些有关PAF1C基本科学问题的研究成果将使我们理解PAF1C本身的装配机理及调节组蛋白修饰和调控基因表达的分子机制，也将揭示PAF1C在细胞生长发育中的作用机理，也会为阐明由于PAF1C功能紊乱而导致的相关疾病的发生发展上提供理论基础和前期积累。

The highly conserved eukaryotic paf1 complex (PAF1C) coordinates regulation of histone modification and recruitment of multiple transcriptional factors, thereby regulating gene expression. PAF1C is a multiprotein complex composed of six subunits. However, the molecular mechanism of the PAF1C assembly and regulation remains elusive. Here, we will use multidisciplinary methods to study the mode of PAF1C assembly and the relationship between structure and function of the complex. We will explore the role of PAF1C in vivo by using model organism yeast and the basis of Rtf1 subunit in recognizing the substrate of histone complex H2A/H2B. Moreover, we will study the molecular mechanism of PAF1C assembly mediated by the scaffold protein Ctr9 and its interaction with various histone modification enzymes. All these findings about the basic scientific questions of PAF1C will enable us to understand the molecular mechanism of PAF1C assembly and its regulation roles in both histone modification and gene expression, will also reveal the mechanism of PAF1C in cell growth and development, and will clarify the developmental process of diseases causing by dysfunction of PAF1C.