ETS1促转录停滞释放和血管新生的分子机制研究

血管系统的功能异常与许多常见疾病如心梗、脑卒中和肿瘤的有着密切的联系。以往研究证明细胞外以及细胞浆内的信号传导分子对于血管发育和功能具有重要影响。然而对细胞核内分子包括转录因子和表观遗传学分子在血管中的功能及作用机制知之甚少。ETS1 是重要的转录因子。ETS1在休眠血管内皮中过表达足以启动血管再生。但是其促血管新生的基本分子机制还不清楚。 本课题拟采用基因组学、转录组学、生物信息学、生物化学和分子生物学以及血管新生动物模型相结合的方法，探讨ETS1调控 RNAPII转录效率和血管再生的分子机制，从而为控制血管新生，进而治疗相关疾病提供新的理论依据和分子靶标。

Aberrant blood vessel development contributes to many types of diseases such as myocardial infarction, stroke and cancer. Decades of intensive studies have revealed that the extracelluar and intracelluar signal transduction pathways that regulate vascular development. However, the transcriptioanl and epigentic program inside the nuclei are less understood. The ETS family of transcrption factor (TF) play key roles in vasculogensis and angiogenesis. ETS1, a prototypical ETS family member, is essential for angiogenesis, and overexpression of ETS1 is sufficient to activate angiogeneiss in quiescent endothelial cells. The fundamental mechanism by which ETS1 activates angiogesis is unkown. Our prelimiary ChiP-seq experiments revealed that ETS1 highly occupanpied the regulatory elements of a broad range of angiogesis-related genes in endothelial cells and regulated their expression and response to VEGF activation. Moreover, ETS1 has been found to regulate RNAPII RNA transcriptional activity. In the study, we propose to futher unveil the molecular mechanism underlying ETS1 regulates angiogenesis and RNA synthesis through the integation of cutting-edge techniques such as ChiP-seq, RNA-seq, protein immunoprecipitation and transgentic mouse etc. The fullarching goal of this study is to open a new avenue to devleop new theories and therapeutic targets controlling angiogenesis and its related diseases.