| First Author | Kaur H | Year | 2026 |
| Journal | Cell Rep | Volume | 45 |
| Issue | 7 | Pages | 117604 |
| PubMed ID | 42364105 | Mgi Jnum | J:389440 |
| Mgi Id | MGI:8370409 | Doi | 10.1016/j.celrep.2026.117604 |
| Citation | Kaur H, et al. (2026) Dynamicity of Topoisomerase 1 binding at super-enhancers regulates TLR-responsive gene expression program in macrophages. Cell Rep 45(7):117604 |
| abstractText | Toll-like receptor (TLR) activation elicits an effective innate immune response by inducing the expression of primary and secondary response genes (PRGs and SRGs). Topoisomerase 1 (TOP1) has emerged as a critical regulator of innate immune responses; however, its mechanism of action remains largely unclear. Here, we demonstrate that the ectopic expression of TOP1 is sufficient to program TLR-response in naive macrophages, and its catalytic activity is essential for inducible gene expression. TOP1 preferentially localizes to super-enhancers, and TLR activation results in the rapid redistribution of TOP1 from resting-state super-enhancers to stimulus-gained super-enhancers, leading to a transcriptional switch. Notably, TOP1 facilitates the recruitment of BRG1 to stimulus-gained super-enhancers. The cooperation between TOP1 and BRG1 enhances the chromatin accessibility at super-enhancers to preferentially regulate the expression of SRGs. These findings establish TOP1 as a transcriptional regulator that links chromatin remodeling at active super-enhancers with inducible gene expression in response to pathogenic stimuli. |
