羧基末端乙酰化修饰调控抑癌蛋白p53转录特异性

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (11): 1577-1582.

羧基末端乙酰化修饰调控抑癌蛋白p53转录特异性

闫晓俊, 徐文彬, 王冬来^*

中国医学科学院基础医学研究所北京协和医学院基础学院医学遗传学系,北京 100005

收稿日期:2021-08-04 修回日期:2021-09-17 发布日期:2021-10-27
通讯作者: *dwang@ibms.pumc.edu.cn
基金资助:
国家自然科学基金(81872311,82073132);北京市自然科学基金(7192126)

Acetylation of carboxyl-terminal domain selectively regulates p53-mediated gene transcriptionn

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

Received:2021-08-04 Revised:2021-09-17 Published:2021-10-27
Contact: *dwang@ibms.pumc.edu.cn

摘要/Abstract

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。

关键词: p53, 乙酰化修饰, 基因转录调控, 肿瘤, 生物信息学分析

Abstract: 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. Conclusions The CTD acetylation may selectively and functionally regulate a subset of p53 target genes.

Key words: p53, acetylation, gene transcriptional regulation, tumor, bioinformatic analysis

中图分类号:

R394.3

闫晓俊, 徐文彬, 王冬来. 羧基末端乙酰化修饰调控抑癌蛋白p53转录特异性[J]. 基础医学与临床, 2021, 41(11): 1577-1582.

YAN Xiao-jun, XU Wen-bin, WANG Dong-lai. Acetylation of carboxyl-terminal domain selectively regulates p53-mediated gene transcriptionn[J]. Basic & Clinical Medicine, 2021, 41(11): 1577-1582.

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