{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE295nnn/GSE295530/"]},"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=GSE295530"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"MeCP2 stabilizes the glucocorticoid system in active chromatin regions [RNA-seq]","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":"GSE295530","cross_references":{"GSM":["GSM8952350","GSM8952359","GSM8952117","GSM8952238","GSM8952239","GSM8952118","GSM8952119","GSM8952113","GSM8952234","GSM8952355","GSM8952235","GSM8952114","GSM8952356","GSM8952236","GSM8952357","GSM8952115","GSM8952116","GSM8952237","GSM8952358","GSM8952351","GSM8952230","GSM8952110","GSM8952231","GSM8952352","GSM8952111","GSM8952232","GSM8952353","GSM8952354","GSM8952112","GSM8952233","GSM9931298","GSM9931299","GSM9931296","GSM9931297","GSM8952348","GSM8952106","GSM8952227","GSM8952228","GSM8952107","GSM8952349","GSM8952229","GSM8952108","GSM8952109","GSM8952102","GSM8952223","GSM9931294","GSM8952344","GSM9931295","GSM8952345","GSM8952103","GSM8952224","GSM9931292","GSM8952225","GSM8952346","GSM8952104","GSM8952226","GSM8952105","GSM8952347","GSM9931293","GSM8952340","GSM9931290","GSM8952220","GSM8952341","GSM9931291","GSM8952342","GSM8952100","GSM8952221","GSM8952222","GSM8952343","GSM8952101","GSM8952216","GSM8952337","GSM8952338","GSM8952217","GSM8952339","GSM8952218","GSM8952219","GSM8952212","GSM8952333","GSM8952213","GSM8952334","GSM8952335","GSM8952214","GSM8952215","GSM8952336","GSM8952330","GSM8952331","GSM8952210","GSM8952332","GSM8952211","GSM8952209","GSM8952205","GSM8952326","GSM8952206","GSM8952327","GSM8952328","GSM8952207","GSM8952208","GSM8952329","GSM8952322","GSM8952201","GSM8952202","GSM8952323","GSM8952203","GSM8952324","GSM8952325","GSM8952204","GSM8952320","GSM8952200","GSM8952321","GSM9931388","GSM9931389","GSM9931386","GSM9931387","GSM9931384","GSM9931385","GSM8952319","GSM8952315","GSM8952316","GSM8952317","GSM8952318","GSM8952311","GSM9931382","GSM8952312","GSM9931383","GSM9931380","GSM8952313","GSM9931381","GSM8952314","GSM8952310","GSM9931379","GSM9931498","GSM9931377","GSM9931378","GSM9931499","GSM9931375","GSM9931496","GSM9931497","GSM9931376","GSM9931373","GSM9931494","GSM9931374","GSM9931495","GSM8952308","GSM8952309","GSM8952304","GSM8952305","GSM8952306","GSM8952307","GSM8952300","GSM9931371","GSM9931492","GSM9931493","GSM9931372","GSM8952301","GSM8952302","GSM9931490","GSM8952303","GSM9931491","GSM9931370","GSM9931289","GSM9931287","GSM9931288","GSM9931285","GSM9931286","GSM9931399","GSM9931397","GSM9931398","GSM9931395","GSM9931396","GSM8952403","GSM8952404","GSM9931393","GSM8952400","GSM9931394","GSM9931391","GSM8952401","GSM8952402","GSM9931392","GSM9931390","GSM8951999","GSM9931500","GSM9931501","GSM9931508","GSM9931509","GSM9931506","GSM9931507","GSM9931504","GSM9931505","GSM9931502","GSM9931503","GSM9931401","GSM9931522","GSM9931523","GSM9931402","GSM9931520","GSM9931521","GSM9931400","GSM9931409","GSM9931407","GSM9931528","GSM9931408","GSM9931529","GSM9931526","GSM9931405","GSM9931527","GSM9931406","GSM9931524","GSM9931403","GSM9931404","GSM9931525","GSM9931511","GSM9931512","GSM9931510","GSM9931519","GSM9931517","GSM9931518","GSM9931515","GSM9931516","GSM9931513","GSM9931514","GSM8952094","GSM9931600","GSM8952095","GSM8952096","GSM8952097","GSM8952090","GSM8952091","GSM8952092","GSM8952093","GSM9931601","GSM8952098","GSM8952099","GSM8952083","GSM8952084","GSM8952085","GSM8952086","GSM8952080","GSM8952081","GSM8952082","GSM8952087","GSM8952088","GSM8952089","GSM8952193","GSM9931467","GSM9931588","GSM8952072","GSM9931346","GSM8952073","GSM8952194","GSM9931347","GSM9931468","GSM9931589","GSM9931344","GSM8952074","GSM9931465","GSM9931586","GSM8952195","GSM9931587","GSM8952196","GSM9931345","GSM8952075","GSM9931466","GSM9931584","GSM9931342","GSM9931463","GSM9931464","GSM9931343","GSM9931585","GSM8952190","GSM9931461","GSM8952070","GSM8952191","GSM9931582","GSM9931340","GSM9931341","GSM9931462","GSM8952071","GSM8952192","GSM9931583","GSM9931348","GSM9931469","GSM9931349","GSM9931580","GSM9931581","GSM9931460","GSM8952197","GSM8952076","GSM8952077","GSM8952198","GSM8952199","GSM8952078","GSM8952079","GSM9931335","GSM9931456","GSM8952182","GSM9931577","GSM8952061","GSM8952062","GSM8952183","GSM9931336","GSM9931578","GSM9931457","GSM9931333","GSM9931454","GSM8952184","GSM9931575","GSM8952063","GSM9931576","GSM8952185","GSM9931334","GSM8952064","GSM9931455","GSM9931573","GSM9931452","GSM9931331","GSM9931332","GSM9931453","GSM9931574","GSM9931450","GSM8952180","GSM9931571","GSM9931330","GSM9931451","GSM8952181","GSM8952060","GSM9931572","GSM9931339","GSM9931458","GSM9931579","GSM9931337","GSM9931338","GSM9931459","GSM8952069","GSM9931570","GSM8952065","GSM8952186","GSM8952187","GSM8952066","GSM8952188","GSM8952067","GSM8952068","GSM8952189","GSM8952050","GSM8952171","GSM8952292","GSM9931368","GSM9931489","GSM8952051","GSM9931369","GSM8952293","GSM8952172","GSM8952173","GSM9931487","GSM8952294","GSM8952052","GSM9931366","GSM8952053","GSM8952174","GSM9931367","GSM9931488","GSM8952295","GSM9931364","GSM9931485","GSM9931365","GSM9931486","GSM9931362","GSM9931483","GSM8952290","GSM9931484","GSM8952291","GSM9931363","GSM8952170","GSM9931481","GSM8952179","GSM8952058","GSM9931360",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