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题名

ZFHX3通过组蛋白修饰调控肝癌发生发展的机制研究

姓名
姓名拼音
ZHENG Yaohan
学号
11930124
学位类型
硕士
学位专业
0710 生物学
学科门类/专业学位类别
学术型::07 理学
导师
董金堂
导师单位
人类细胞生物和遗传学系
论文答辩日期
2022-04-27
论文提交日期
2022-06-16
学位授予单位
南方科技大学
学位授予地点
深圳
摘要

在不同肿瘤中,转录因子锌指同源异形框3ZFHX3)的调控作用不同。探究ZFHX3在肿瘤发生中的功能和机制对于肿瘤的诊断和治疗具有重要意义。肝细胞癌(HCC)是最常见的原发性肝癌,是世界上癌症死亡的重要原因。HCC关键基因的组蛋白修饰模式与HCC的发生发展密切相关。本课题致力于探索ZFHX3HCC中通过影响表观遗传方面的组蛋白修饰调控肿瘤发生发展的功能,并试图揭示ZFHX3通过调控染色质重塑调控组蛋白修饰变化的分子机制。

方法:通过免疫共沉淀-质谱分析(IP-MS),免疫共沉淀联合免疫印迹(IP-western blot),以及蛋白质与染色质结合紧密程度的实验来检测ZFHX3与染色质域解旋酶DNA结合蛋白4CHD4)的相互结合,以及ZFHX3CHD4与染色质结合紧密程度的调控作用。利用免疫印迹实验检测ZFHX3对组蛋白修饰的调控作用,并构建低氧诱导模型检测ZFHX3对于组蛋白修饰的调控作用是否受到低氧环境的影响。

结果与结论:转录因子ZFHX3与染色质重塑解旋酶CHD4具有相互作用,沉默ZFHX3增强CHD4与染色质的结合紧密程度,提示CHD4ZFHX3的结合以及CHD4与染色质的结合可能存在竞争关系。在ZFHX3对组蛋白修饰的调控作用方面,敲减ZFHX3能够减弱H3K4me3H3K36me3以及总的乙酰化修饰水平。H3K4me3H3K36me3发挥激活转录的功能,在肝癌中敲减CHD4能够降低总的H3K4me3的表达水平。上述结果提示,在肝癌中,ZFHX3通过调控CHD4与染色质的结合程度来影响靶基因的组蛋白修饰水平,进而调控靶基因的转录。

 

 

关键词
语种
中文
培养类别
独立培养
入学年份
2019
学位授予年份
2022-07
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条目标识符http://sustech.caswiz.com/handle/2SGJ60CL/335855
专题南方科技大学医学院
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郑瑶涵. ZFHX3通过组蛋白修饰调控肝癌发生发展的机制研究[D]. 深圳. 南方科技大学,2022.
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