转录因子OCT-4对靶基因AP-2γ表达调控的研究

The Regulation of Downstream Target Gene AP-2γ by Transcription Factor OCT-4

OCT-4和AP-2γ是近年来睾丸生殖细胞瘤诊断过程中研究的热点基因.作为一个在胚胎发育中起着重要作用的转录因子,OCT-4基因在发育的不同时期、不同分化过程中发挥着多种生物学功能,其作用是通过对靶基因的调控来实现的.本研究运用多种软件分析,发现AP-2γ启动子区域的序列部分有OCT-4的结合位点.利用CHIP-PCR方法鉴定AP-2γ是OCT-4调控的靶基因.应用Luciferase assay、免疫荧光实验、小鼠隐睾模型等实验进行验证,OCT-4基因抑制AP-2γ转录活性和影响其蛋白质水平的表达.这一新发现,有利于从分子水平上研究睾丸生殖细胞瘤的发生机制.

In recent years,OCT-4 and AP-2γ have been widely used as clinical markers of testicular germ cell tumors.Transcription factor OCT-4,which plays an important role in embryonic development,gives full play to a variety of biological functions in different developmental periods and differentiations.The effect of OCT-4 is realized through the regulation of the target genes.In this study,we found OCT-4 binding sites within the sequence of AP-2γ promoter region by a variety of bionemerics.AP-2γ,a novel target gene of OCT-4,was identified by chromatin immunoprecipitation（ChIP）-PCR.A combination of sequence analysis,reporter gene assays,Western blot,immunofluorescence assay and mouse cryptorchidism model experiment further confirmed that AP-2γ was the target gene of OCT-4.OCT-4 inhibited the transcriptive activity of AP-2γ.The expression of AP-2γ gene was confirmed to be significantly altered by silencing or overexpression of OCT-4.This new discovery is conductive to study the malignant process of germ cell tumors at the molecular level.