GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE252nnn/GSE252737/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE252737GEOGSEfalseIL-4 Exploits TNF signaling to Shape Its Signature Gene Expression in Human Monocytes. [ChIP-Seq]Investigation of crosstalk between antagonistic pro- and anti-inflammatory cytokines has focused on mechanisms and functional consequences of cross-inhibition. We investigated cross-regulation between proinflammatory TNF and anti-inflammatory IL-4 in primary human monocytes and in a skin wound-healing model. Surprisingly, TNF functioned mainly as a costimulator of IL-4-induced gene expression, whereas IL-4 selectively inhibited the TNF-induced IFN response, leaving inflammatory gene expression mostly intact. TNF and IL-4 synergistically induced gene sets important for regulating inflammation and tissue repair, which were highly induced during the phase of wound healing when these cytokines are co-expressed. Crosstalk between TNF and IL-4 was mediated by epigenetic chromatin-mediated mechanisms associated with cooperation between NF-κB and STAT6 transcription factors, erasure of negative histone mark H3K27me3, and selective inhibition of IRF1. These results identify a long-sought mechanism for expansion of the IL-4 response, and highlight the complexity of crosstalk between antagonistic cytokines that includes cooperation for select gene responses important in immune response and tissue repair.2026/09/03GSE252737GSM8006072GSM8006073GSM8006074GSM8006075GSM8006070GSM8006071GSM8006117GSM8006118GSM8006119GSM8006113GSM8006114GSM8006115GSM8006116GSM8006076GSM8006110GSM8006077GSM8006078GSM8006111GSM8006112GSM8006079GSM8006083GSM8006084GSM8006085GSM8006086GSM8006080GSM8006081GSM8006082GSM8006128GSM8006129GSM8006124GSM8006125GSM8006126GSM8006127GSM8006087GSM8006120GSM8006121GSM8006088GSM8006089GSM8006122GSM8006123GSM8006050GSM8006051GSM8006052GSM8006053GSM8006058GSM8006059GSM8006054GSM8006055GSM8006056GSM8006057GSM8006061GSM8006062GSM8006063GSM8006064GSM8006060GSM8006106GSM8006107GSM8006108GSM8006109GSM8006069GSM8006102GSM8006103GSM8006104GSM8006105GSM8006065GSM8006066GSM8006067GSM8006100GSM8006101GSM8006068GSM8006030GSM8006031GSM8006036GSM8006037GSM8006038GSM8006039GSM8006032GSM8006033GSM8006034GSM8006035GSM8006040GSM8006041GSM8006042GSM8006047GSM8006048GSM8006049GSM8006043GSM8006044GSM8006045GSM8006046GSM8006094GSM8006095GSM8006096GSM8006130GSM8006097GSM8006090GSM8006091GSM8006092GSM8006093GSM8006139GSM8006135GSM8006136GSM8006137GSM8006138GSM8006098GSM8006131GSM8006132GSM8006099GSM8006133GSM8006134GSM8006140GSM8006141GSM8006029GSM8006025GSM8006026GSM8006027GSM8006028GSM8006021GSM8006142GSM8006143GSM8006022GSM8006144GSM8006023GSM8006024167911857324676252737Homo sapiens