Institute of Biochemistry, Justus-Liebig-University, D-35392 Giessen, Germany.
Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University, D-35392 Giessen, Germany.
Cells. 2021 Mar 29;10(4):753. doi: 10.3390/cells10040753.
Activation of the transcription factor NF-κB elicits an individually tailored transcriptional response in order to meet the particular requirements of specific cell types, tissues, or organs. Control of the induction kinetics, amplitude, and termination of gene expression involves multiple layers of NF-κB regulation in the nucleus. Here we discuss some recent advances in our understanding of the mutual relations between NF-κB and chromatin regulators also in the context of different levels of genome organization. Changes in the 3D folding of the genome, as they occur during senescence or in cancer cells, can causally contribute to sustained increases in NF-κB activity. We also highlight the participation of NF-κB in the formation of hierarchically organized super enhancers, which enable the coordinated expression of co-regulated sets of NF-κB target genes. The identification of mechanisms allowing the specific regulation of NF-κB target gene clusters could potentially enable targeted therapeutic interventions, allowing selective interference with subsets of the NF-κB response without a complete inactivation of this key signaling system.
转录因子 NF-κB 的激活会引发个体定制的转录反应，以满足特定细胞类型、组织或器官的特殊需求。基因表达的诱导动力学、幅度和终止的控制涉及核内 NF-κB 调节的多个层次。在这里，我们讨论了在不同水平的基因组组织中，我们对 NF-κB 和染色质调节剂之间相互关系的理解的一些最新进展。在衰老或癌细胞中发生的基因组 3D 折叠的变化可能会导致 NF-κB 活性的持续增加。我们还强调了 NF-κB 参与形成层次组织的超级增强子的作用，这使得 NF-κB 靶基因的共同调控集的协调表达成为可能。确定允许 NF-κB 靶基因簇特异性调节的机制可能能够实现靶向治疗干预，允许选择性干扰 NF-κB 反应的子集，而不会完全抑制这个关键信号系统。
