E2F作为一种重要的转录因子在细胞周期进程中发挥着非常重要的作用。它调节了许多重要的细胞周期相关基因的转录。DNA复制在细胞中受到了精确的调控，每个细胞周期基因组DNA都只能复制一次。在DNA复制过程中DNA聚合酶δ的作用最为重要，其催化亚基p125在细胞中的表达具有细胞周期依赖性。本论文研究工作为E2F对POLD1基因的转录调控机理提供了初步的依据，丰富了POLD1基因的转录调控研究。为今后进一步深入的研究提供了基础。本论文中主要通过染色体免疫共沉淀证明了E2F1与E2F4在细胞内能够与POLD1的启动子结合并能以促进型转录因子的作用调节p125的表达。同时能够促进POLD1启动子的转录活性。将细胞同步化后分析结果显示两种转录因子都在G1/S期与POLD1启动子结合水平最高。为了进一步研究这种转录调控作用，向细胞中转染了p21使细胞内的p21表达水平提高，发现p21影响了细胞中E2F1与POLD1启动子的结合情况，抑制了E2F1与POLD1启动子的结合，但对E2F4与POLD1启动字的结合没有明显影响。同时p21能够抑制E2F1、E2F4对POLD1启动子活性的促进作用。推测E2F4可能以一种不同的方式对POLD1进行着转录调控作用。使用抗肿瘤药物阿霉素处理细胞发现该药物降低了细胞中DNA聚合酶δ催化亚基p125的蛋白表达水平。进一步的实验表明，阿霉素通过提高p21水平及对E2F1蛋白表达的抑制进一步抑制了POLD1的转录水平。

As a transcription factor, E2F plays a very important role in cell cycle. It regulates transcription of many important cell cycle related genes. DNA replication is tightly controlled in cells. DNA is exactly doubled only once in one cell cycle. Of many kinds of DNA polymerases, DNA polymerase delta is the most important one in the process of DNA replication. The expression of its catalytic subunit p125 is cell-cycle dependent. In this thesis, these results provide a basic evidence for mechanism of POLD1 gene transcription regulation and are helpful for further research.In this thesis, chromatin immunoprecipitation was used. It’s found that E2F1 and E2F4 bind to the promoter of POLD1 gene in the cell and regulate the transcription of POLD1 gene.To further study the regulation of transcription, plasmids were transfected into MCF7 cells to express p21. It’s found that p21 inhibits the binding of E2F1 to the promoter of POLD1 gene, but has no effect on the binding of E2F4 to the POLD1 promoter. This effect and other people’s study provide that p21 affect the transcription level of the POLD1 gene indirectly through E2F1.Doxorubisin(DOX) was used to treat the MCF7 cell and it’s found that DOX inhibits the expression level of p125 in the cell. Further study demonstrated that DOX inhibits the expression of E2F1 and improve the expression of p21 which combine together to inhibit the expression of p125.