{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE273nnn/GSE273993/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Mus musculus"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE273993"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Nuclear receptor Nur77 resolves the inflammatory response of macrophages primarily by cis- and trans-regulation of AP-1 target genes [ChIP-Seq]","description":"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.","dates":{"publication":"2026/07/28"},"accession":"GSE273993","cross_references":{"GSM":["GSM8441221","GSM8441220","GSM8441227","GSM8441205","GSM8441226","GSM8441204","GSM8441207","GSM8441206","GSM8441228","GSM8441223","GSM8441222","GSM8441203","GSM8441225","GSM8441224","GSM8441219","GSM8441210","GSM8441216","GSM8441215","GSM8441218","GSM8441217","GSM8441212","GSM8441211","GSM8441214","GSM8441213","GSM8441209","GSM8441208"],"GPL":["34290"],"GSE":["273993"],"taxon":["Mus musculus"]}}