摘要
目的探究在非小细胞肺癌细胞系H1299中,p53羧基末端(CTD)乙酰化修饰是否特异性调控基因转录,分析p53 CTD乙酰化修饰潜在的生物学功能。方法在p53表达缺失的H1299细胞中构建可诱导表达野生型p53(p53-WT)或模拟CTD乙酰化修饰p53(p53-6KQ)的稳转细胞株;以doxycycline(Doxy)处理诱导稳转细胞株,表达外源性p53-WT或p53-6KQ,通过全转录组测序结合生物学信息分析,表征p53 CTD乙酰化修饰特异性调控的基因及其潜在的生物学功能。结果获得可诱导表达p53的质粒和稳转细胞株;筛选出306个p53-6KQ特异性调控的差异表达基因,发现这些基因主要与细胞命运决定、基因转录调控、神经元发育、肿瘤坏死因子信号通路等生物学过程有关。结论CTD乙酰化修饰可以特异性调控p53对某些下游基因的转录,进而调节某些生物学过程。
Objective To explore whether carboxyl-terminal domain(CTD)acetylation contributes to selectively regulating p53-mediated transcription of a subset of genes.Methods Based on p53-null lung cancer cell line H1299,a pair of inducible cell strains expressing the wildtype p53(p53-WT)and the CTD acetylation-mimicking p53(p53-6KQ)were constructal,respectively,and a response to doxycycline(Doxy)treatment was generated.RNA-sequencing was applied to analyze the changes of the transcriptional profiles regulated by p53-WT or p53-6KQ.Bio-informatic analysis was performed to annotate p53-6KQ-specific candidates,and their potential biological functions.Results The p53-inducible cell strains were successfully established.306 differentially expressed genes that were specifically regulated by p53-6KQ were identified.These genes were functionally enriched in the biological processes involving in cell fate determination,transcription,neuron development and tumor necrosis factor signaling pathway.ConclusionsThe CTD acetylation may selectively and functionally regulate a subset of p53 target genes.
作者
闫晓俊
徐文彬
王冬来
YAN Xiao-jun;XU Wen-bin;WANG Dong-lai(Department of Medical Genetics, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China)
出处
《基础医学与临床》
2021年第11期1577-1582,共6页
Basic and Clinical Medicine
基金
国家自然科学基金(81872311,82073132)
北京市自然科学基金(7192126)。
