申请者发现了SAMD11是EYA的协同转录因子；意外地了解到该基因存在45种选择性剪接变体（其中四种剪接变体不遵循传统的GT-AG规则），且这种特性在物种间相对保守；更令人兴奋的结果是：在高糖模型细胞中，SAMD11的mRNA和蛋白表达量都显著增加，提示SAMD11可能参与糖尿病视网膜病变（糖网）的发生发展。迄今为止，未见SAMD11功能的报道。.本课题拟用蛋白复合体沉淀、ChIP 测序（ChIP-Seq）和表达谱分析等方法，以SAMD11与蛋白、DNA相互作用为主要研究对象，全局性地分析SAMD11的功能及调控网络（顺式作用元件及反式作用因子、相互作用的蛋白、所调控的下游通路、所结合的启动子、选择性剪接变体的功能）；揭示其在糖网发生发展中的分子机制，发现糖网通路的新成员或阐明新的糖网通路，寻找治疗糖网的新靶点，为可能的早期诊断、治疗或干预方案提供分子依据。

We found SAMD11 was the transcriptional co-activator of EYA. In the process of cloning full coding regions of SAMD11, we identified 45 SAMD11 alternative splice (AS) variants. Interestingly, 4 AS variants didn't obey the "GT-AG" rule. Among those 115 sequenced clones, ASV5 (20 out of 115) and ASV6 (26 out of 115) were the most dominant forms. ASV5 underwent AS events of E7c (139-186, E7) skipping and I6b (143-145, I6) retention; ASV6 yielded to I6b retention. Analysis of 98 ESTs related to human SAMD11 not only showed the wide expression of SAMD11 in different tissues, but also validated and enriched SAMD11 AS events that had been found. 96 ESTs related to mouse Samd11 indicated the existence of AS variants in mouse and the conservation of SAMD11 AS variants between human and mouse. Expression analysis by real-time PCR showed high expression of SAMD11 in 3 ocular cell lines (Y79, RPE, HCE) and 293T cells, while relatively low expression in HREC, HL-60 and SHI-1 cell lines. RT-PCR analysis revealed that the expression patterns of SAMD11 AS variants were similar in Y79 and 293T cells, while distinguished in other cells... Further analysis showed significantly increased expression of SAMD11 in diabetic retinopathy (DR) cell model, both in mRNA and protein levels, which indicated the important functions of SAMD11 in the pathogenesis of DR. To date, only one article focuses on mouse Samd11, there is no research on human SAMD11 function, let alone the roles of SAMD11 play in the pathogenesis of DR. Thus, to throw light on the pathology of DR, it is exigent to figure out the basic functions of SAMD11 at first...This study will focus on the interactions between SAMD11 and proteins, DNA, and analyzinge the functions and regulatory networks of SAMD11 with global view by the means of protein complex precipitation, ChIP-Seq, gene-expression profiling, etc. The analysis contents include proteins interact with SAMD11, signaling pathways downstream of SAMD11, promoters bound by SAMD11, regulation of SAMD11 expression, functions of SAMD11 AS variants, etc. The aim of this study is to reveal the functions of SAMD11 in the pathogenesis of DR, and to interfere, even block, development of DR by regulating the SAMD11 signaling pathway and interaction networks, and to provide molecular underpinnings for early diagnosis, treatment and intervention of DR.