基因组足迹揭示了无处不在的因素的细胞类型特定DNA结合
P B Becker1, S Ruppert, G Schütz
1Institute of Cell and Tumor Biology, German Cancer Research Center, Heidelberg, Federal Republic of Germany.
Cell
|November 6, 1987
概括
通过阻止蛋白质结合,DNA甲基化使氨酸转移酶 (TAT) 基因沉默,即使存在DNA结合因子,也会阻止蛋白质结合. 这种表观遗传修饰控制了肝瘤细胞中的基因表达.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因规则 基因规则
背景情况:
- 氨酸转移酶 (TAT) 基因在表达细胞和非表达细胞中表现出改变的染色质结构.
- 了解蛋白质-DNA相互作用对于阐明基因调节机制至关重要.
研究的目的:
- 研究TAT基因调控区域中的蛋白-DNA相互作用.
- 确定影响肝瘤细胞TAT基因表达的因素.
主要方法:
- 在体内测量二甲基硫酸盐足迹以绘制蛋白质-DNA接触的地图.
- 在体外DNAase I足迹分析以分析特定的DNA结合因子.
- 基因组测序以检测DNA甲基化模式.
主要成果:
- 蛋白与DNA的接触仅在表达TAT的细胞中发现.
- 在表达细胞和非表达细胞中都存在DNA结合因子.
- 在非表达细胞中CpG二核酸甲基化与体内蛋白质结合的缺失相关.
- 在体外甲基化抑制了与DNA结合的因子.
结论:
- 基因甲基化,特别是在CpG二核酸中,是抑制TAT基因的关键机制.
- 仅仅DNA结合因子的存在就不足以激活基因;通过甲基化调节的DNA可访问性至关重要.
- 表观遗传修饰在控制组织特异性基因表达方面发挥着至关重要的作用.
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