Stepwise modifications of transcriptional hubs link pioneer factor activity to a burst of transcription.
Stepwise modifications of transcriptional hubs link pioneer factor activity to a burst of transcription.
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DOI：
10.1038/s41467-023-40485-6
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发表时间：
2023-08-10
影响因子：
16.6
通讯作者：
O'Farrell, Patrick H.
中科院分区：
文献类型：
--
作者：
Cho, Chun-Yi;O'Farrell, Patrick H.
转录因子（TF）的结合促进了随后的辅激活因子和前起始复合物的募集，以启动真核转录，但这一时间过程通常是不可见的。通常认为，募集的因子最终共同存在于更高级的结构中，允许远距离结合的TF激活核心启动子处的转录。我们使用的内源性标记的蛋白质，包括先驱TF塞尔达，共激活dBrd4，和RNA聚合酶II（RNAPII）的实时成像，以确定在早期果蝇胚胎转录起始上游的事件级联。这些因子在非组蛋白基因的激活过程中顺序地和瞬时地募集到离散的簇。Zelda和乙酰转移酶dCBP使dBrd4簇成核，然后触发RNAPII的转录前簇。随后的转录延伸分散dBrd4和RNAPII的簇。我们的研究结果表明，真核转录因子的转录激活涉及一系列不同的生物分子凝聚物，最终在一个自限性的转录爆发。真核转录涉及亚核枢纽的形成，其丰富了转录机制。在这里，作者表明，枢纽经历逐步修改，以燃料的转录爆发，而不是有一个稳定的组成。
Binding of transcription factors (TFs) promotes the subsequent recruitment of coactivators and preinitiation complexes to initiate eukaryotic transcription, but this time course is usually not visualized. It is commonly assumed that recruited factors eventually co-reside in a higher-order structure, allowing distantly bound TFs to activate transcription at core promoters. We use live imaging of endogenously tagged proteins, including the pioneer TF Zelda, the coactivator dBrd4, and RNA polymerase II (RNAPII), to define a cascade of events upstream of transcriptional initiation in early Drosophila embryos. These factors are sequentially and transiently recruited to discrete clusters during activation of non-histone genes. Zelda and the acetyltransferase dCBP nucleate dBrd4 clusters, which then trigger pre-transcriptional clustering of RNAPII. Subsequent transcriptional elongation disperses clusters of dBrd4 and RNAPII. Our results suggest that activation of transcription by eukaryotic TFs involves a succession of distinct biomolecular condensates that culminates in a self-limiting burst of transcription. Eukaryotic transcription involves the formation of subnuclear hubs that enrich transcriptional machinery. Here the authors show that the hubs undergo stepwise modifications to fuel a burst of transcription rather than having a stable composition.
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