转录因子凝结介质集群MET 调节和增强基因表达中的基因表达
James Lee1,2, Leman Simpson2,3, Yi Li1,2
1Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, 16802, USA.
bioRxiv : the preprint server for biology
|February 19, 2024
概括
转录因子 (TFs) 形成凝结物来调节基因. 在酵母中,Met4和Met32形成核凝聚物,聚合目标基因,在饥饿时增强甲氨酸生物合成基因表达.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 转录因子 (TF) 可以经历液-液相分离 (LLPS) 形成凝结物.
- 在3D基因组组织和基因调节中,TF凝结物的作用尚未完全被理解.
- 发芽酵母中的甲 (甲) 饥饿诱导了甲生物合成的基因,由TF Met4和Met32.2等联合激活剂调节.
研究的目的:
- 为了研究酵母酵母中Met4和Met32凝结物的形成和功能.
- 确定这些凝结物在3D基因组组织和基因调节中在甲胺饥饿期间的作用.
主要方法:
- 在酵母核中观察内源的Met4和Met32局部化.
- 在实验室中对复合Met4和Met32相分离特性进行表征.
- 分析Met4点与目标基因的同定位和3D染色质聚类的分析.
- 使用MET3pr-GFP记者和具有截断内在失调区域 (IDR) 的Met4突变体评估记者基因活性和转录调节.
主要成果:
- 内源的Met4和Met32在甲素耗尽时形成共同局部化的核点.
- 再组合的Met4和Met32在体外表现出LLPS特性,形成混合滴.
- Met4 puncta与目标基因共同定位,这些基因以一种依赖Met4的方式在3D中聚集在一起.
- 一名MET3pr-GFP记者显示,与Met4点的增强活动和同定位.
- 一个具有部分IDR截断的Met4突变体显示了减少的点形成,并选择性地减少了记者活动.
结论:
- Met4和协同激活剂形成核凝聚物,促进多个目标基因的聚类.
- 这些凝结物增加了局部TF度,使得对 metionin 枯竭的强有力的转录反应成为可能.
- TF驱动的LLPS在组织基因组和调节基因表达以响应环境线索方面发挥着至关重要的作用.
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