Galouzis Charalampos Chrysovalantis, Kherdjemil Yacine, Forneris Mattia, Viales Rebecca R, Marco-Ferreres Raquel, Furlong Eileen E M
European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany.
European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany.
Mol Cell. 2025 Jun 19;85(12):2425-2441.e9. doi: 10.1016/j.molcel.2025.05.018. Epub 2025 Jun 9.
The cofactor LIM-domain-binding protein 1 (Ldb1) is linked to many processes in gene regulation, including enhancer-promoter communication, interchromosomal interactions, and enhanceosome-cofactor-like activity. However, its functional requirement and molecular role during embryogenesis remain unclear. Here, we used optogenetics (iLEXY) to rapidly deplete Drosophila Ldb1 (Chip) from the nucleus at precise time windows. Remarkably, this pinpointed the essential window of Chip's function to just 1 h of embryogenesis, overlapping zygotic genome activation (ZGA). We show that Zelda, a pioneer factor essential for ZGA, recruits Chip to chromatin, and both factors regulate concordant changes in gene expression, suggesting that Chip is a cofactor of Zelda. Chip does not significantly impact chromatin architecture at these stages, but instead recruits CBP, and is essential for H3K27ac deposition at enhancers and promoters, and for the proper expression of co-regulated genes. These data identify Chip as a functional bridge between Zelda and the coactivator CBP to regulate gene expression in early embryogenesis.
辅助因子LIM结构域结合蛋白1（Ldb1）与基因调控中的许多过程相关联，包括增强子-启动子通讯、染色体间相互作用以及增强体-辅助因子样活性。然而，其在胚胎发生过程中的功能需求和分子作用仍不清楚。在此，我们使用光遗传学（iLEXY）在精确的时间窗口内将果蝇Ldb1（Chip）从细胞核中快速耗尽。值得注意的是，这将Chip功能的关键窗口精确到仅胚胎发生的1小时，与合子基因组激活（ZGA）重叠。我们表明，Zelda是ZGA所必需的先驱因子，它将Chip招募到染色质上，并且这两个因子共同调节基因表达的一致性变化，这表明Chip是Zelda的辅助因子。在这些阶段，Chip对染色质结构没有显著影响，而是招募CBP，并且对于增强子和启动子处H3K27ac的沉积以及共同调控基因的正确表达至关重要。这些数据确定Chip是Zelda与共激活因子CBP之间的功能桥梁，以在早期胚胎发生中调节基因表达。
