{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE298nnn/GSE298418/"]},"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=GSE298418"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"MeCP2 stabilizes the glucocorticoid system in active chromatin regions [CUT&Tag]","description":"Methyl-CpG-binding protein 2 (MeCP2), a key epigenetic factor regulating gene expression via DNA/chromatin interactions, causes Rett syndrome when dysfunctional. However, its regulatory mechanisms at the pan-tissue and multi-omics levels remain poorly understood. Here, we constructed comprehensive pan-tissue transcriptional profiles and chromatin accessibility profiles from wild-type and Mecp2-knockout mice. Integrative analyses revealed that glucocorticoid (GC)-induced genes (GIGs) exhibited global hyperactivation following Mecp2 knockout, highlighting a crucial role for MeCP2 in maintaining GC signaling homeostasis. Through innovative single-cell multi-omics profiling of the nervous system, we found that GIG dysregulation primarily disrupts neural homeostasis via non-neuronal cells. Mechanistically, we uncovered a dual regulatory mode of MeCP2: (1) competitively limiting NR3C1 occupancy at GIG cis-regulatory elements in active chromatin regions, and (2) specifically disrupting NR3C1-NCOA1 coactivator interactions. Importantly, pharmacologically suppressing aberrant GC system activation ameliorated pathological phenotypes and significantly prolonged survival in Mecp2-knockout mice. Our study demonstrates the critical pathological role of hyperactivated GC signaling in the multisystem disturbances of Mecp2-knockout mice and suggests potential therapeutic targets for Rett syndrome.","dates":{"publication":"2026/07/31"},"accession":"GSE298418","cross_references":{"GSM":["GSM9014029","GSM9014028","GSM9014027","GSM9014026","GSM9014025","GSM9014024","GSM9014023","GSM9014022","GSM9014021","GSM9014020","GSM9014019","GSM9014018","GSM9014017","GSM9014016","GSM9014015","GSM9014014","GSM9014013","GSM9014012","GSM9014011","GSM9014010","GSM9013999","GSM9014009","GSM9013998","GSM9014008","GSM9013997","GSM9014007","GSM9013996","GSM9014006","GSM9013995","GSM9014005","GSM9013994","GSM9014004","GSM9013993","GSM9013992","GSM9014003","GSM9014002","GSM9013991","GSM9014001","GSM9013990","GSM9014044","GSM9014000","GSM9014043","GSM9014042","GSM9014041","GSM9014040","GSM9931283","GSM9931284","GSM9931281","GSM9931282","GSM9013989","GSM9013988","GSM9013987","GSM9013986","GSM9014039","GSM9014038","GSM9014037","GSM9014036","GSM9014035","GSM9014034","GSM9014033","GSM9014032","GSM9014031","GSM9014030"],"GPL":["28330","34290"],"GSE":["298418"],"taxon":["Mus musculus"]}}