Differentiating neutrophils undergo large-scale changes in nuclear morphology. How such alterations in structure are established and modulated upon exposure to microbial agents is largely unknown. Here, we found that prior to encounter with bacteria, an armamentarium of inflammatory genes was positioned in a transcriptionally passive environment suppressing premature transcriptional activation. Upon microbial exposure, however, human neutrophils rapidly (<3 h) repositioned the ensemble of proinflammatory genes toward the transcriptionally permissive compartment. We show that the repositioning of genes was closely associated with the swift recruitment of cohesin across the inflammatory enhancer landscape, permitting an immediate transcriptional response upon bacterial exposure. We found that activated enhancers, marked by increased deposition of H3K27Ac, were highly enriched for cistromic elements associated with PU.1, CEBPB, TFE3, JUN, and FOSL2 occupancy. These data reveal how upon microbial challenge the cohesin machinery is recruited to an activated enhancer repertoire to instruct changes in chromatin folding, nuclear architecture, and to activate an inflammatory gene program.

中文翻译：

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在受到微生物挑战后，人类中性粒细胞的核结构和染色质折叠会发生快速变化，从而编排即时的炎症基因程序。

分化的中性粒细胞的核形态发生大规模变化。在暴露于微生物制剂时，这种结构的改变是如何建立和调节的在很大程度上尚不清楚。在这里，我们发现在遇到细菌之前，炎症基因的武器库位于转录被动环境中，抑制过早的转录激活。然而，在接触微生物后，人类中性粒细胞迅速（<3小时）将促炎基因群重新定位到转录允许的区室。我们表明，基因的重新定位与炎症增强剂景观中粘连蛋白的快速募集密切相关，从而允许在细菌暴露后立即发生转录反应。我们发现，以 H3K27Ac 沉积增加为标志的活化增强子高度富集与 PU.1、CEBPB、TFE3、JUN 和 FOSL2 占据相关的顺反子元素。这些数据揭示了在微生物挑战时，粘连蛋白机制如何被招募到激活的增强子库中，以指导染色质折叠、核结构的变化，并激活炎症基因程序。