转录因子二分化激活了p300乙转移酶
Esther Ortega1, Srinivasan Rengachari1,2, Ziad Ibrahim1,3
1European Molecular Biology Laboratory, Grenoble, France.
Nature
|October 17, 2018
概括
转录因子二分化通过转自化激活p300联合激活剂. 这一过程涉及一个关键的氨酸循环,调节基因表达和染色体乙化.
科学领域:
- 分子生物学
- 表观遗传学
- 蛋白质生物化学
背景情况:
- p300 是转录的协同激活剂和基因表达至关重要的酸转移酶 (HAT).
- 通过乙化染色体,主要在转录增强剂中发挥p300的作用.
- 通过信号通路控制p300激活的精确机制仍然不完全理解.
研究的目的:
- 阐明转录因子配体激活p300的分子机制.
- 调查转录因子二分化在p300激活中的作用.
- 通过其配体来表征p300激活的结构基础.
主要方法:
- 使用模型转录因子IRF3和STAT1.
- 进行生物化学测试以研究p300激活和乙化.
- 确定了p300的晶体结构,包括激活反应的中间体.
主要成果:
- 转录因子二分化对于p300的激活至关重要.
- 在自抑制循环中触发p300的转自乙化.
- 晶体结构显示了跨自乙化的中间状态,并突出显示了RING域的作用.
结论:
- 它的转录因子配体的激活和寡合化直接控制p300的激活.
- 这些发现解释了细胞信号,转录因子活性和染色体乙化之间的联系.
- 这种机制为基因转录如何在表观遗传层面上受到调节提供了洞察力.
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