Acute MeCP2 loss in adult mice reveals transcriptional and chromatin changes that precede neurological dysfunction and inform pathogenesis.

ABSTRACT: Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene cause Rett syndrome, a severe childhood neurological disorder. MeCP2 is a well-established transcriptional repressor, yet upon its loss, hundreds of genes are dysregulated in both directions. To understand what drives such dysregulation, we deleted Mecp2 in adult mice, circumventing developmental contributions and secondary pathogenesis. We performed time series transcriptional, chromatin, and phenotypic analyses of the hippocampus to determine the immediate consequences of MeCP2 loss and the cascade of pathogenesis. We find that loss of MeCP2 causes immediate and bidirectional progressive dysregulation of the transcriptome. To understand what drives gene downregulation, we profiled genome-wide histone modifications and fo

SUBMITTER: Bajikar SS 

PROVIDER: S-EPMC11802321 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature