美国威尔康奈尔医学院Olivier Elemento、Ari M. Melnick等研究人员合作发现，OCT2的预定位促进体液免疫的细胞命运转变和染色质结构改变。相关论文于2021年9月23日在线发表在《自然—免疫学》杂志上。

在体液免疫反应期间，研究人员绘制了染色质可及性图谱，并表明OCT2是与生发中心（GC）调控元件不同可及性相关的主导转录因子。沉默的染色质区域注定要成为GC特异性的超级增强子（SE），在初始B细胞（NB）中含有预置的OCT2结合点。这些预置的SE"种子"以富含OCT2 DNA结合模体调控元件的空间聚集为特征，这些元件在GC B细胞（GCB）中被OCT2及其GC特异性共激活因子OCAB大量加载。

具有高丰度预定位OCT2结合的SE在GC中优先形成长距离染色质接触，从而促进GC特异性因子的表达。这些区域的可及性和结构互动性的提高取决于OCAB的招募。将关键调控因子预置在SE可能是一种广泛使用的策略，从而促进细胞命运的快速转变。

据介绍，在GC反应期间，B细胞经历了深刻的转录、表观遗传和基因组结构变化。这种变化是如何建立的仍然是未知的。

附：英文原文

Title: OCT2 pre-positioning facilitates cell fate transition and chromatin architecture changes in humoral immunity

Author: Doane, Ashley S., Chu, Chi-Shuen, Di Giammartino, Dafne Campigli, Rivas, Martn A., Hellmuth, Johannes C., Jiang, Yanwen, Yusufova, Nevin, Alonso, Alicia, Roeder, Robert G., Apostolou, Effie, Melnick, Ari M., Elemento, Olivier

Issue&Volume: 2021-09-23

Abstract: 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.

DOI: 10.1038/s41590-021-01025-w

Source: https://www.nature.com/articles/s41590-021-01025-w