{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317131/"]},"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"," Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317131"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"CpG content determines tissue-resident macrophage enhancer selection","description":"Tissue-resident macrophages (TRMs) acquire specialized identities through transcription factor (TF) networks operating in distinct chromatin environments. Early growth response 2 (EGR2) contributes both to alveolar macrophage (AM) identity and to interleukin (IL)-4-driven polarization of bone marrow-derived macrophages (BMDMs), yet the regulatory principles enabling its function across these contexts remain unclear. By integrating RNA-seq and ATAC-seq data from wild-type and Egr2-deficient macrophages, we show that macrophage identity is constrained by DNA methylation-dependent cis-regulatory landscapes. AM-specific enhancers are predominantly CpG-rich and hypomethylated, a feature shared with additional TRM populations, whereas BMDM-accessible regulatory regions are largely CpG-poor. Although IL-4 induces EGR2 together with KLF4 and DEC1 in BMDMs, this TF module fails to engage CpG-rich enhancers, indicating that the BMDM regulatory network lacks additional AM-specific components required for their activation. These findings identify CpG content as a determinant of enhancer competence and provide a mechanistic explanation for the context-dependent activity of EGR2 in macrophages, placing macrophage plasticity under the control of sequence-encoded epigenetic constraints.","dates":{"publication":"2026/07/28"},"accession":"GSE317131","cross_references":{"GSM":["GSM9465532","GSM9465543","GSM9465542","GSM9465531","GSM9465534","GSM9465545","GSM9465544","GSM9465533","GSM9465547","GSM9465536","GSM9465535","GSM9465546","GSM9465538","GSM9465527","GSM9465537","GSM9465548","GSM9465541","GSM9465530","GSM9465540","GSM9465529","GSM9465539","GSM9465528"],"GPL":["19057","30172"],"GSE":["317131"],"taxon":["Mus musculus"]}}