DNA探针拉下查揭示了O-GlcNAcylation转录因子DNA相互作用的调制
Guofang Li1,2, Fanxu Meng1,2, Xiaomin Zhong3
1Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, Shenyang, China.
Scientific reports
|July 2, 2025
概括
较高的O结合β-N-乙糖胺 (O-GlcNAc) 水平增强了包括转录因子在内的众多核蛋白的DNA结合. 这项研究揭示了O-GlcNAcylation的存在.
科学领域:
- 分子生物学分子生物学
- 后翻译修改 后翻译修改
- 基因规则 基因规则
背景情况:
- 与O相关的β-N-乙糖胺 (O-GlcNAc) 是一种对调节基因表达至关重要的核转化后修饰.
- O-GlcNAcylation调节转录因子 (TF) 活性,但其对蛋白质-DNA相互作用在全蛋白质基因范围内的影响尚不清楚.
研究的目的:
- 研究O-GlcNAcylation水平对内源核蛋白的DNA结合效率的影响,特别是转录因子和辅助因子.
- 开发和应用定量蛋白质学方法来评估O-GlcNAcylation对蛋白质-DNA相互作用的影响.
主要方法:
- 使用共识TF响应元素 (catTFRE) 的下拉选方法.
- 定量蛋白质组学用于识别受O-GlcNAcylation影响的核蛋白 (NP) 和TF/辅因子.
- 在活细胞中对特定的Forkhead家族TF进行验证.
主要成果:
- 升高的O-GlcNAcylation显著增强了241个核蛋白的DNA结合.
- O-GlcNAcylation的升高增强了146个TFs/辅助因子的DNA结合.
- 特定的叉头TFs (例如FOXA1,FOXC1) 显示在活细胞中对O-GlcNAcylation进行增强的DNA结合.
结论:
- O-GlcNAcylation 在调节蛋白质-DNA相互作用方面发挥着重要作用.
- 开发的方法提供了一种有效的方式来评估O-GlcNAcylation对转录调节的影响.
- 这项研究加深了对O-GlcNAcylation在调节基因表达中的作用的理解.
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