GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333477/primaryOK200Genomics Mus musculusHomo sapiensGenome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333477GEOGSEfalseDynamicity of Topoisomerase 1 binding at super-enhancers regulates TLR-responsive gene expression program in macrophagesToll-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 ectopic expression of TOP1 is sufficient to program TLR-response in naïve macrophages and its catalytic activity is essential for inducible gene expression. TOP1 preferentially localizes to super-enhancers and TLR activation results in 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 an epigenomic regulator that links chromatin remodeling at active super-enhancers with inducible gene expression in response to pathogenic stimuli.2026/05/28GSE333477GSM9765740GSM9765741GSM9765732GSM9765699GSM9765733GSM9765734GSM9765735GSM9765736GSM9765737GSM9765738GSM9765739GSM9765691GSM9765692GSM9765693GSM9765694GSM9765695GSM9765696GSM9765730GSM9765697GSM9765698GSM9765731GSM9765690GSM9765729GSM9765721GSM9765688GSM9765722GSM9765689GSM9765723GSM9765724GSM9765725GSM9765726GSM9765727GSM9765728GSM9765680GSM9765681GSM9765682GSM9765683GSM9765684GSM9765685GSM9765686GSM9765687GSM9765720GSM9765718GSM9765719GSM9765710GSM9765677GSM9765678GSM9765711GSM9765712GSM9765679GSM9765713GSM9765714GSM9765715GSM9765716GSM9765717GSM9765670GSM9765671GSM9765672GSM9765673GSM9765674GSM9765675GSM9765676GSM9765707GSM9765708GSM9765709GSM9765666GSM9765667GSM9765700GSM9765701GSM9765668GSM9765669GSM9765702GSM9765703GSM9765704GSM9765705GSM9765706GSM9765660GSM9765661GSM9765662GSM9765663GSM9765664GSM9765665GSM9765655GSM9765656GSM9765657GSM9765658GSM9765659GSM9765650GSM9765651GSM9765652GSM9765653GSM9765654GSM9765644GSM9765645GSM9765646GSM9765647GSM9765648GSM9765649GSM9765640GSM9765641GSM9765642GSM9765643GSM9765636GSM9765637GSM9765638GSM9765639170212467624247333477 Mus musculusHomo sapiens