The Expression of p16 is Regulated by The Reversible Histone Acetylation
The Expression of p16 is Regulated by The Reversible Histone Acetylation
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p16的表达受可逆组蛋白乙酰化的调节
DOI：
10.3724/sp.j.1206.2009.00722
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发表时间：
2010
影响因子：
0.3
通讯作者：
Zhao Jing
中科院分区：
文献类型：
--
作者：
Wang Xiu-Li;Huang Bai-Qu;Feng Yun-Peng;Lu Jun;Zhang Guo-Ping;Pan Hong;Zhao Jing
p16 INK 4a通过负调控CDK 4/6的活性而在细胞周期进程的控制中起关键作用。结果表明，组蛋白乙酰转移酶p300对p16 INK 4a启动子的激活有促进作用，而组蛋白去乙酰化酶HDAC 3/4则抑制p300介导的p16 INK 4a启动子的激活，降低p16 INK 4a mRNA和蛋白水平。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.