P-TEFb识别并调控特异基因转录延伸重启机制

转录延伸重启已被认为是调控应激性基因转录表达的新模式，正性转录延伸因子P-TEFb在调控基因转录延伸重启中扮演关键角色，但目前对P-TEFb识别、募集和调控特异基因转录延伸重启的机制还一无所知。我们的前期结果提示：中介体亚基动态乙酰化修饰可能与P-TEFb识别特异基因有关，且可能以双P-TEFb分子协同作用的模式来调控延伸重启。本项目拟通过探讨中介体亚基的动态乙酰化修饰机制及其对P-TEFb募集的调控作用，来了解P-TEFb识别特异基因的机制，并通过鉴定P-TEFb的两条募集通道及其各自的作用靶点，以揭示P-TEFb调控转录延伸重启的模式。期望能阐明P-TEFb识别并调控特异基因转录延伸重启的机制，为基因转录调控新模式的确立提供理论依据。

The transcription elongation stage has been regarded as a noval platform for the regulation of gene expression. As a positive transcription elongation factor, P-TEFb plays a dispensable role in regulating the transition of paused transcription elongation. However, how P-TEFb recognizes and is recruited to those stimulation-specific genes is still unclear. Our previous data suggest that the dynamic acetylated subunits of Mediator might be the fundation for P-TEFb to recognize those specific genes and the transition of paused elongation might be regulated by the cooperation of two P-TEFb molecules. Therefore, we will study the acetylation mechanism of Mediator subunits and their roles in P-TEFb recruitment, and identify the recruitment pathways of P-TEFbs and their targetings. We expect to reveal how P-TEFb recognizes specific genes and regulates their transcription elongation resuming, thereby providing deep insight into the mechanism of P-TEFb in regulating specific gene expression.