转录因子与NIPBL/MAU2形成三元复合体,以在增强剂上定位凝聚蛋白
Gregory Fettweis1, Kaustubh Wagh2, Diana A Stavreva2
1Laboratory of Gene Expression and Cancer, GIGA-Molecular & Computational Biology, University of Liège, 4000 Liège, Belgium.
bioRxiv : the preprint server for biology
|December 23, 2024
概括
通过转录因子相互作用来调解NIPBL蛋白质定位到特定的DNA位点. 在NIPBL中的两个LxxLL基因集群调节其功能和与凝聚体加载体复合体 (NIPBL/MAU2) 和类固醇受体的相互作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 凝聚蛋白复合体对基因组架构至关重要,但其特定的局部化机制仍然不清楚.
- 转录因子相互作用被假设为指导凝聚力加载器复合体 (NIPBL/MAU2) 增强区域.
研究的目的:
- 在NIPBL中确定控制其本地化和功能的监管要素.
- 阐明NIPBL与包括类固醇受体在内的转录因子相互作用的分子机制.
主要方法:
- 在NIPBL序列中识别和描述LxxLL图案.
- 生物化学试验研究NIPBL-MAU2异构体的形成和稳定性.
- 结构生物学技术 (AlphaFold2) 和分子对接以建模蛋白质复合体.
- 对NIPBL-MAU2与葡萄糖皮质体受体 (GR) 和其他转录因子相互作用的分析.
主要成果:
- 在NIPBL中确定了两个不同的LxxLL图案集群,调节其动态和互动组.
- 一个集群对于NIPBL-MAU2异构体稳定性至关重要.
- 第二个群集调解了与类固醇受体连接体结合域的特定结合,以GR为例.
- 在结构上建模了GR-NIPBL-MAU2的三元复合体,突出了它在GR-依赖基因调节中的作用.
- 多个转录因子被证明通过不同的接口与NIPBL-MAU2相互作用.
结论:
- NIPBL的LxxLL动机对于其与凝聚力加载器组件MAU2和转录因子的相互作用至关重要.
- 这些相互作用有助于将凝聚体复合物招募到特定的基因组位置,从而影响转录程序.
- 这些发现为转录因子如何通过凝聚性局部化指导基因组架构提供了分子基础.
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