During developmental progression the genomes of immune cells undergo large-scale changes in chromatin folding. However, insights into signaling pathways and epigenetic control of nuclear architecture remain rudimentary. Here, we found that in activated neutrophils calcium influx rapidly recruited the cohesin-loading factor NIPBL to thousands of active enhancers and promoters to dictate widespread changes in compartment segregation. NIPBL recruitment to enhancers and promoters occurred with distinct kinetics. The induction of NIPBL-binding was coordinate with increased P300, BRG1 and RNA polymerase II occupancy. NIPBL-bound enhancers were associated with NFAT, PU.1, and CEBP cis elements, whereas NIPBL-bound promoters were enriched for GC-rich DNA sequences. Using an acute degradation system, we found that the histone acetyltransferases P300 and CBP maintained H3K27ac abundance and facilitated NIPBL occupancy at enhancers and that active transcriptional elongation is essential to maintain H3K27ac abundance. Chromatin remodelers, containing either of the mutually exclusive BRG1 and BRM ATPases, promoted NIPBL recruitment at active enhancers. Conversely, at active promoters, depletion of BRG1 and BRM showed minimal effect on NIPBL occupancy. Finally, we found that calcium signaling in both primary innate and adaptive immune cells swiftly induced NIPBL occupancy. Collectively, these data reveal how transcriptional regulators, histone acetyltransferases, chromatin remodelers, and transcription elongation promote NIPBL occupancy at active enhancers while the induction of NIPLB occupancy at promoters is primarily associated with GC-rich DNA sequences.

中文翻译：

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钙信号通过不同的机制指示活性增强子和启动子处的 NIPBL 募集，以重建基因组区室化

在发育过程中，免疫细胞的基因组会发生染色质折叠的大规模变化。然而，对核结构的信号通路和表观遗传控制的见解仍然不成熟。在这里，我们发现在活化的中性粒细胞中，钙离子流入迅速将黏附素加载因子 NIPBL 招募到数千个活性增强子和启动子中，以指示隔室分离的广泛变化。NIPBL 向增强子和启动子的募集以不同的动力学发生。NIPBL 结合的诱导与 P300、BRG1 和 RNA 聚合酶 II 占有率的增加相协调。NIPBL 结合增强子与 NFAT、PU.1 和 CEBP顺式相关元素，而 NIPBL 结合的启动子富含 GC 的 DNA 序列。使用急性降解系统，我们发现组蛋白乙酰转移酶 P300 和 CBP 维持 H3K27ac 丰度并促进 NIPBL 在增强子的占用，并且主动转录延伸对于维持 H3K27ac 丰度至关重要。染色质重塑剂，包含相互排斥的 BRG1 和 BRM ATPases，促进 NIPBL 在活性增强剂处的募集。相反，在活性启动子上，BRG1 和 BRM 的消耗对 NIPBL 占用率的影响很小。最后，我们发现初级先天性和适应性免疫细胞中的钙信号迅速诱导 NIPBL 占据。总的来说，这些数据揭示了转录调节因子、组蛋白乙酰转移酶、染色质重塑剂、