GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE295nnn/GSE295530/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE295530GEOGSEfalseMeCP2 stabilizes the glucocorticoid system in active chromatin regions [RNA-seq]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.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musculus