The study investigates the molecular mechanisms underlying neurological disorders caused by mutations in the *MECP2* gene, which encodes methyl-CpG binding protein 2 (MeCP2). Using gene expression analysis in the hypothalamus of *MECP2*-null and overexpressing mice, the researchers found that MeCP2 dysfunction leads to changes in the expression levels of thousands of genes, with the majority (~85%) being activated by MeCP2. The study confirmed that MeCP2 binds to the promoters of six selected genes and associates with the transcriptional activator CREB1 at the promoter of an activated target but not a repressed target. These findings suggest that MeCP2 regulates a wide range of genes in the hypothalamus and can function as both an activator and repressor of transcription. The study also highlights the importance of MeCP2 in neuronal function and provides insights into the molecular mechanisms underlying *MECP2* disorders, such as Rett syndrome and related neurological conditions.The study investigates the molecular mechanisms underlying neurological disorders caused by mutations in the *MECP2* gene, which encodes methyl-CpG binding protein 2 (MeCP2). Using gene expression analysis in the hypothalamus of *MECP2*-null and overexpressing mice, the researchers found that MeCP2 dysfunction leads to changes in the expression levels of thousands of genes, with the majority (~85%) being activated by MeCP2. The study confirmed that MeCP2 binds to the promoters of six selected genes and associates with the transcriptional activator CREB1 at the promoter of an activated target but not a repressed target. These findings suggest that MeCP2 regulates a wide range of genes in the hypothalamus and can function as both an activator and repressor of transcription. The study also highlights the importance of MeCP2 in neuronal function and provides insights into the molecular mechanisms underlying *MECP2* disorders, such as Rett syndrome and related neurological conditions.