组蛋白高乙酰化促进大鼠C6胶质瘤细胞中GDNF基因启动子Ⅱ区RNA POLⅡ的募集  

Histone hyperacetylation promotes the recruitment of RNA POLⅡin the promoterⅡof GDNF gene in rat C6 glioma cells

作　　者：郭庭文 张宝乐 李亚东 倪海波[3] 曾振林 线春明[1] GUO Tingwen;ZHANG Baole;LI Yadong;NI Haibo;ZENG Zhenlin;XIAN Chunming(Department of Neurosurgery,Qinghai Provincal People's Hospital,Qinghai Xining 810000,China;Department of Biology,Xuzhou Medical University,Jiangsu Xuzhou 221004,China;Department of Neurosurgery,the First People's Hospital of Zhangjiagang City,Jiangsu Suzhou 215600,China)

机构地区：[1]青海省人民医院神经外科,青海西宁810000 [2]徐州医科大学生物学教研室,江苏徐州221004 [3]张家港市第一人民医院神经外科,江苏苏州215600

出　　处：《现代肿瘤医学》2022年第19期3472-3476,共5页Journal of Modern Oncology

摘　　要：目的:探讨大鼠C6胶质瘤细胞中胶质细胞源性神经营养因子(GDNF)启动子Ⅱ区组蛋白高乙酰化引起该基因高转录的机制。方法:采用ChIP-PCR技术检测了大鼠C6星形胶质瘤细胞和正常星形胶质细胞中GDNF启动子I区和Ⅱ区RNA POLⅡ的募集量;利用ChIP-PCR技术,检测组蛋白乙酰基转移酶抑制剂姜黄素(Curcumin)和去乙酰化酶抑制剂曲古抑菌素A(TSA)处理C6胶质瘤细胞对GDNF启动子I区和Ⅱ区RNA POLⅡ募集的影响。结果:正常星形胶质细胞和C6胶质瘤细胞中GDNF启动子I区RNA POLⅡ募集量无明显差异;同正常星形胶质细胞相比,C6胶质瘤细胞中GDNF启动子Ⅱ区RNA POLⅡ募集量显著升高。当Curcumin显著降低C6胶质瘤细胞中GDNF启动子Ⅱ区组蛋白乙酰化水平时,RNA POLⅡ募集量显著下调(P<0.05);而当TSA显著升高GDNF启动子Ⅱ区组蛋白乙酰化水平时,RNA POLⅡ募集量显著升高(P<0.05)。结论:在大鼠C6胶质瘤细胞中,GDNF启动子Ⅱ区组蛋白高乙酰化介导的RNA POLⅡ募集量升高可能是其高转录的原因。Objective:To investigate the mechanism by which histone hyperacetylation in the promoterⅡof GDNF(glial cell line-derived neurotrophic factor)gene in rat C6 glioma cells causes high transcription of the GDNF.Methods:ChIP-PCR was used to detect the recruitment of RNA POLⅡin the promoter I andⅡof the GDNF gene in rat C6 astroglioma cells and normal astrocytes.After C6 glioma cells were treated with histone acetyltransferase inhibitor Curcumin or deacetylase inhibitor trichostatin A(TSA),ChIP-PCR was used to explore recruitment of RNA POLⅡin the promoter I andⅡof the GDNF gene.Results:There was no significant difference in recruitment of RNA POLⅡin the promoter I of the GDNF gene between normal astrocytes and C6 glioma cells.Compared with that in normal astrocytes,the recruitment of RNA POLⅡin promoterⅡof the GDNF gene,increased significantly in C6 glioma cells.When Curcumin significantly reduced the level of histone acetylation in promoterⅡof the GDNF gene in C6 glioma cells,the recruitment of RNA POLⅡwas significantly down-regulated(P<0.05).When TSA significantly increased the level of histone acetylation inpromoterⅡof the GDNF gene in C6 glioma cells,the recruitment of RNA POLⅡincreased significantly(P<0.05).Conclusion:In C6 glioma cells,the increased recruitment of RNA POLⅡmediated by histone hyperacetylation in promoterⅡof the GDNF gene may be the reason for high transcription.

关 键 词：GDNF 启动子 乙酰化 RNA POLⅡ 胶质瘤 

分 类 号：R730.264[医药卫生—肿瘤]