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. 2021 Mar 25;12:655590. doi: 10.3389/fimmu.2021.655590

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Copyright © 2021 Fernando, Sciumè, O’Shea and Shih

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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A model of rapid gene induction in NK cells through higher-order chromatin architecture and remodeling. Many inducible genes in NK cells are associated with super-enhancers (SEs) that can be orderly modulated by multi-dimensional epigenetic mechanisms (72). (A) Phase separation. Phase separation occurs as a dynamic process in which transcription factors (TFs) and co-activators form non-membrane bound condensates through weak multivalent protein-protein interactions of their intrinsically disordered region (130). Multi-loop hubs bring TF-bound regulatory elements (REs) and their target genes into close proximity to finetune gene expression. (B) Super-enhancers (SEs). SEs differ from typical enhancers as they recruit large numbers of TFs and transcriptional apparatus, including co-activators, to drive high magnitude of gene induction (130–132). (C) Topologically associating domains (TADs). Hi-C plots allow for visualization of three-dimensional TADs and sub-TADs, which form during the cohesin-mediated loop extrusion process. Looping can occur between two convergently oriented CCCTC-binding factor (CTCF) sites, using a cohesin ring that extrudes DNAs as shown in (A) (2, 133–135).