通过DNA引导的转录因子相互作用扩展了人类的基因调节代码
Zhiyuan Xie1, Ilya Sokolov2,3, Maria Osmala4
1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Nature
|April 9, 2025
概括
研究人员绘制了人类转录因子 (TF) 之间的相互作用,以了解基因调节代码. 他们发现了成千上万的TF-TF相互作用和新的复合动机,揭示了细胞命运和发育的洞察力.
科学领域:
- 基因组学
- 分子生物学
- 系统生物学
背景情况:
- 与DNA结合的转录因子 (TFs) 形成基因调节代码,对细胞命运和转录程序至关重要.
- 人类的基因调节是复杂的,涉及超过1600个相互作用的TF,但它们与DNA结合的相互作用仍然不清楚.
研究的目的:
- 绘制DNA结合的人类转录因子之间的生化相互作用.
- 同时确定TF-TF结合偏好,相互作用和结合的DNA序列.
- 通过互动的TF对形成的新型复合图案.
主要方法:
- 使用CAP-SELEX (细胞阵列处理 - 通过指数式丰富对联体的系统演化),是一种高吞吐量方法.
- 选了超过58,000个转录因子-转录因子对,以确定相互作用对及其DNA结合偏好.
主要成果:
- 确定了2,198个互动的TF对,其中1,329个对特定的模式有偏好的结合.
- 发现了1131种新的TF-TF复合图案,与单个TF图案不同.
- 据估计,镜识别了所有人类TF-TF图案的18%至47%.
结论:
- 新型复合基因富含细胞类型特异性元素,活跃在体内,并且经常在发育共同表达的TF之间形成.
- 定义胚胎轴的TF之间的相互作用解释了类似的TF如何在这些轴上指定不同的细胞类型.
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