{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE299nnn/GSE299346/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299346"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Mecp2 stabilizes the glucocorticoid system in active chromatin regions [scRNA-Seq]","description":"Methyl-CpG-binding protein 2 (MECP2), a key epigenetic factor regulating gene expression via DNA/chromatin interactions, causes multisystem disorders when dysfunctional. However, its epigenetic regulatory mechanisms at the pan-tissue and multi-omics levels remain poorly understood. Here, we established comprehensive pan-tissue expression profiles in wild-type and Mecp2-knockout mice, revealing a crucial role for MECP2 in maintaining glucocorticoid (GC) signaling homeostasis. Single-cell epigenomic analyses demonstrated widespread increases in chromatin accessibility at GC-induced genes (GIGs) upon Mecp2 deficiency. Through innovative single-cell multi-omics profiling of the nervous system, we further revealed that GIG dysregulation primarily disrupts neural homeostasis via non-neuronal cells. Mechanistically, we identified a dual regulatory mode of MECP2: (1) competitively inhibiting NR3C1 binding to the cis-regulatory elements of GIGs in active chromatin regions, and (2) specifically disrupting NR3C1-NCOA1 coactivator interactions. These findings not only elucidate a novel MECP2-NR3C1-NCOA1 axis in GC system regulation but also suggest potential therapeutic targets for Rett syndrome.","dates":{"publication":"2026/07/31"},"accession":"GSE299346","cross_references":{"GSM":["GSM9037702","GSM9037701","GSM9037704","GSM9037703","GSM9037687","GSM9037686","GSM9037689","GSM9037700","GSM9037688","GSM9037683","GSM9037682","GSM9037685","GSM9037684","GSM9037681","GSM9037680","GSM9037679","GSM9037698","GSM9037676","GSM9037697","GSM9037678","GSM9037711","GSM9037710","GSM9037699","GSM9037677","GSM9037694","GSM9037693","GSM9037696","GSM9037695","GSM9037690","GSM9037692","GSM9037691","GSM9037709","GSM9037706","GSM9037705","GSM9037708","GSM9037707"],"GPL":["28330"],"GSE":["299346"],"taxon":["Mus musculus"]}}