GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326173/primary200OKGenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326173GEOGSEfalseNuclear receptor Nur77 resolves the inflammatory response of macrophages primarily by regulating expression of AP-1 transcription factors and their target genes [ChIP-seq]The nuclear receptor Nur77 plays a crucial, protective role in chronic inflammatory diseases and deficiency of Nur77 in macrophages results in excessive pro-inflammatory cytokine secretion. Previous research suggested that Nur77's regulatory function in inflammation is due to repression of the pro-inflammatory transcription factor NF-ĸB, but the underlying mechanism remains unclear. To address this, we applied a genome-wide, multi-omics approach in LPS-stimulated RAW264.7 macrophages with inducible Nur77 expression. Key findings were validated in wild-type and Nur77-deficient bone marrow-derived macrophages. We show that Nur77 suppresses the expression of inflammatory genes through a dual mechanism wherein Nur77 acts as a repressor of AP-1 targets at two levels: First, Nur77 occupies regulatory elements proximal to AP-1 target genes through AP-1 motifs and second, Nur77 regulates the expression of AP-1 family members themselves. These repressive activities of Nur77 result in diminished RNA Pol II on AP-1 genes and their targets. The first zinc finger of the Nur77 DNA-binding domain is required to reduce AP-1 activity. In summary, Nur77 represses macrophage inflammation through regulation of both immediate-early AP-1 expression, as well as inhibition of AP-1-driven gene programs.2026/07/28GSE326173GSM9624570GSM9624571GSM9624538GSM9624539GSM9624536GSM9624558GSM9624559GSM9624537GSM9624574GSM9624552GSM9624553GSM9624575GSM9624572GSM9624550GSM9624573GSM9624551GSM9624556GSM9624557GSM9624576GSM9624554GSM9624577GSM9624555GSM9624560GSM9624549GSM9624569GSM9624547GSM9624548GSM9624563GSM9624541GSM9624542GSM9624564GSM9624561GSM9624562GSM9624540GSM9624545GSM9624567GSM9624568GSM9624546GSM9624565GSM9624543GSM9624566GSM962454434290326173Mus musculus