GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325918/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325918GEOGSEfalseNuclear receptor Nur77 resolves the inflammatory response of macrophages primarily by regulating expression of AP-1 transcription factors and their target genes [RNA-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.2026/07/28GSE325918GSM9617219GSM9617217GSM9617218GSM9617237GSM9617215GSM9617216GSM9617238GSM9617213GSM9617235GSM9617236GSM9617214GSM9617233GSM9617211GSM9617234GSM9617212GSM9617231GSM9617210GSM9617232GSM9617230GSM9617208GSM9617209GSM9617228GSM9617207GSM9617229GSM9617226GSM9617227GSM9617224GSM9617225GSM9617222GSM9617223GSM9617220GSM961722134290325918Mus musculus