Notch在多种肿瘤的进展中起关键作用。在哺乳动物中有四个Notch基因，Notch1-4。四种Notch在胰腺癌细胞中都有表达。但是它们的作用有何不同，为何不同？尚不清楚。Notch蛋白质虽是转录因子但并不直接结合DNA。我们推测：（1）四种Notch蛋白质所调控靶基因的不同是其生物学作用不同的重要机制；（2）这些不同是因为它们在胞内段结构域（RAM、ANK等）上存在着差异；（3）这些结构上的差异使不同的Notch结合不同的效应转录因子，从而作用于不同的基因区域和发挥不用的调控作用。在本研究中，我们用CHIP-Seq测定四个Notch蛋白质及其潜在的效应转录因子如CSL、ETS1、ZNF143、RUNX3等在基因组的结合位点，以找出每个Notch蛋白质在基因组的调控区域，和了解其与不同效应转录因子的互作情况。通过本研究，我们将阐明四种Notch蛋白质在胰腺癌细胞基因组的靶基因和调控细节。

Notch family proteins play important roles in the progression of many cancers. There are four different Notch genes in mammalian cells. Four Notch proteins, Notch1-4 are all expressed in pancreatic cancer cells. But It is still not known what's difference among different Notch proteins in term of their biological functions, and why they have different biological effects. Notch proteins lack DNA binding domain thus not directly bind to DNA. We hypothesize that:(1) Notch proteins have different biological functions may partially because they have different genome binding patterns; (2) They bind to different genomic regions because the structures of their intra-cellular domains are different; (3) Because the difference among their intracellular domains, they recruit different effecter transcription factors (CSL, ETS1,ZNF143, RUNX3, etc.)and thus bind and regulate different genes. In the present study, we will use CHIP-Seq to capture whole-genome wide binding sites of Notch proteins and their potential effecter transcription factors, and find interactions between Notch family proteins and effecter transcription factors. We will figure out targeting gene profile and regulatory mechanism in pancreatic cancer cell genome for all four Notch proteins.