During the germinal center (GC) reaction, B cells undergo profound transcriptional, epigenetic and genomic architectural changes. How such changes are established remains unknown. Mapping chromatin accessibility during the humoral immune response, we show that OCT2 was the dominant transcription factor linked to differential accessibility of GC regulatory elements. Silent chromatin regions destined to become GC-specific super-enhancers (SEs) contained pre-positioned OCT2-binding sites in naive B cells (NBs). These preloaded SE ‘seeds’ featured spatial clustering of regulatory elements enriched in OCT2 DNA-binding motifs that became heavily loaded with OCT2 and its GC-specific coactivator OCAB in GC B cells (GCBs). SEs with high abundance of pre-positioned OCT2 binding preferentially formed long-range chromatin contacts in GCs, to support expression of GC-specifying factors. Gain in accessibility and architectural interactivity of these regions were dependent on recruitment of OCAB. Pre-positioning key regulators at SEs may represent a broadly used strategy for facilitating rapid cell fate transitions.

在生发中心 (GC) 反应期间，B 细胞会经历深刻的转录、表观遗传和基因组结构变化。这种变化是如何建立的仍然未知。在体液免疫反应期间映射染色质可及性，我们表明 OCT2 是与 GC 调节元件的差异可及性相关的主要转录因子。注定要成为 GC 特异性超增强子 (SEs) 的沉默染色质区域在幼稚 B 细胞 (NBs) 中包含预先定位的 OCT2 结合位点。这些预加载的 SE“种子”具有空间聚集的调节元件，这些元件富含 OCT2 DNA 结合基序，这些基序在 GC B 细胞 (GCB) 中大量加载 OCT2 及其 GC 特异性共激活因子 OCAB。具有高丰度预置 OCT2 结合的 SE 优先在 GC 中形成远程染色质接触，支持 GC 特定因子的表达。这些区域的可访问性和建筑交互性的提高取决于 OCAB 的招募。在 SE 预先定位关键监管机构可能代表一种广泛使用的促进快速细胞命运转变的策略。