Laboratory for Cell Systems, Institute for Protein Research, Osaka University, Yamadaoka, Suita, Osaka, Japan.
Cellular Informatics Laboratory, RIKEN, Wako, Saitama, Japan.
PLoS Genet. 2022 Jun 1;18(6):e1010235. doi: 10.1371/journal.pgen.1010235. eCollection 2022 Jun.
The transcription factor NF-κB, which plays an important role in cell fate determination, is involved in the activation of super-enhancers (SEs). However, the biological functions of the NF-κB SEs in gene control are not fully elucidated. We investigated the characteristics of NF-κB-mediated SE activity using fluorescence imaging of RelA, single-cell transcriptome and chromatin accessibility analyses in anti-IgM-stimulated B cells. The formation of cell stimulation-induced nuclear RelA foci was abolished in the presence of hexanediol, suggesting an underlying process of liquid-liquid phase separation. The gained SEs induced a switch-like expression and enhanced cell-to-cell variability in transcriptional response. These properties were correlated with the number of gained cis-regulatory interactions, while switch-like gene induction was associated with the number of NF-κB binding sites in SE. Our study suggests that NF-κB SEs have an important role in the transcriptional regulation of B cells possibly through liquid condensate formation consisting of macromolecular interactions.
转录因子 NF-κB 在细胞命运决定中发挥重要作用，参与超增强子 (SE) 的激活。然而，NF-κB SE 在基因调控中的生物学功能尚未完全阐明。我们使用抗 IgM 刺激的 B 细胞中的 RelA 荧光成像、单细胞转录组和染色质可及性分析，研究了 NF-κB 介导的 SE 活性的特征。在存在己二醇的情况下，细胞刺激诱导的核 RelA 焦点的形成被消除，这表明存在液-液相分离的潜在过程。获得的 SE 诱导了开关样表达，并增强了转录反应中的细胞间可变性。这些特性与获得的顺式调控相互作用的数量相关，而开关样基因诱导与 SE 中 NF-κB 结合位点的数量相关。我们的研究表明，NF-κB SE 在 B 细胞的转录调控中可能具有重要作用，可能通过包含大分子相互作用的液-固凝聚物形成。
