可逆的组蛋白乙酰化调控p16的表达(英文)  

The Expression of p16 is Regulated by The Reversible Histone Acetylation

作　　者：王秀莉[1] 冯云鹏[1] 赵静[1] 张国平[2] 潘虹[1] 黄百渠[1] 陆军[1] 

机构地区：[1]东北师范大学遗传与细胞研究所,长春130024 [2]广东医学院生物学教研室,东莞523808

出　　处：《生物化学与生物物理进展》2010年第6期600-606,共7页Progress In Biochemistry and Biophysics

基　　金：supported by grants from The National Natural Science Foundation of China (30800557);the Program for Changjiang Scholars and Innovative Research Team (PCSIRT) in Universities(IRT0519)~~

摘　　要：p16INK4a通过抑制CDK4/6的活性而在细胞周期进行中发挥重要的作用,研究发现,组蛋白乙酰转移酶p300能促进p16INK4a启动子活性,而组蛋白去乙酰化酶HDAC3/4能够逆转由p300介导的p16INK4a启动子活性的增加,HDAC3/4能够降低p16INK4amRNA和蛋白质的水平.染色质免疫沉淀(ChIP)实验结果表明转染p300表达质粒能够逆转由HDAC3/4介导的p16INK4a启动子组蛋白的低乙酰化状态.此外,免疫荧光实验结果表明HDAC4的核质穿梭起着重要的作用.免疫印迹和染色质免疫沉淀实验证明HDAC的抑制剂丁酸钠盐(NaBu)能通过诱导组蛋白的高乙酰化而促进p16INK4a的表达.基于这些实验结果,推测出可逆的组蛋白乙酰化参与p16INK4a基因转录调控的模型.p16INK4a plays a key role in control of cell cycle progression by negatively regulating the CDK4/6 activity. It was shown that histone acetyltransferase p300 had a positive effect on the activation of p16INK4a promoter, whereas, histone deacetylases HDAC3/4 counteracted the p300-mediated activation of p16INK4a promoter, and decreased the p16INK4a mRNA and protein levels. Chromatin immunoprecipitation （ChIP） tests revealed that the transfection of p300 reversed the hypoacetylation status of histones at the p16INK4a promoter mediated by HDAC3/4. Moreover, the immunofluorescence study showed that the nucleo-cytoplasmic shuttling of HDAC4 may play an important role. Furthermore, Western blot and ChIP assays demonstrated that the HDAC inhibitor sodium butyrate （NaBu） enhanced p16INK4a expression through inducing histone hyperacetylation. Based on these data, a hypothetical model was proposed for the involvement of reversible histone acetylation in transcriptional regulation of the p16INK4a gene.

关 键 词：P16 P300 HDAC3 HDAC4 可逆的乙酰化 

分 类 号：Q5[生物学—生物化学] Q7