Hh信号通路在动物组织器官发育过程中起到重要作用。Ci/Gli是Hh信号通路核心转录因子，但其自身转录调控的分子机制仍有待揭示。本项目前期研究以遗传筛选为切入点，发现表观遗传因子PRC1的Pc-Sce复合物能直接、正向地调控Ci转录；其功能依赖于PRC2及H3K27me3，但不依赖于Sce连接酶活性；Fsh蛋白与Pc-Sce形成复合物参与Ci转录调控。基于上述研究结果，我们将从分子、细胞和整体动物水平逐级研究Pc-Sce-Fsh复合物如何影响染色质结构而调控Ci/Gli转录，揭示Pc-Sce-Fsh复合物通过表观遗传调控Hh信号通路的分子机制，阐明该复合物在组织器官发育中的功能。项目的实施将回答表观遗传因子如何协同其它转录调控因子共同调控Ci/Gli的转录，进而调控组织器官发育中Hh通路活性的重要发育生物学问题，为最终理解Hh信号通路并为相关疾病的诊治及新的潜在药物靶点的发现提供理论依据。

The evolutionarily conserved Hedgehog (Hh) signaling pathway plays critical functions in development. Dysregulated Hh signaling activity can cause numerous diseases, including medulloblastoma. Cubitus interruptus (Ci) is a critical transcription factor of Hh pathway, which directly controlling the target gene expression in Drosophila. Previous investigations have mainly been focusing on Ci’s stability, localization and transcriptional activity. Yet, the transcriptional regulation of Ci is largely unknown. In our preliminary work, we carried out an RNAi-based genetic screen, and surprisingly found that Pc-Sce of Polycomb Repressive Complex 2 (PRC2) plays a positive role in Ci expression and Hh signal transduction in developing Drosophila wing discs. This finding is inconsistent with previous studies that show Polycomb group (PcG) proteins usually function as repressors of a variety of developmental factors We also found that Pc-Sce binds to the transcription start site (TSS) of Ci in vivo. Interestingly, the PRC2 catalytic activity for H3K27me3, but not the PRC1 catalytic activity for H2AUb1, is required for transcription of Ci. Moreover, Pc-Sce physically and functionally interacts with a well-known transcriptional co-activator Fsh in Ci transcription. In the future study, we will further focus on the molecular mechanism of how Pc-Sce-Fsh complex regulates transcription of Ci, how this complex controls development through Hh signaling both in Drosophila and mouse.