Description
Mutations in methyl-CpG-binding protein 2 (MeCP2) cause Rett syndrome and related autism spectrum disorders. MeCP2 is believed to be required for proper regulation of brain gene expression, but prior microarray studies in Mecp2 knockout mice using brain tissue homogenates have revealed only subtle changes in gene expression. Here, by profiling discrete subtypes of neurons we uncovered more dramatic effects of MeCP2 on gene expression, overcoming the "dilution problem" associated with assaying homogenates of complex tissues. The results reveal misregulation of genes involved in neuronal connectivity and communication. Importantly, genes up-regulated following loss of MeCP2 are biased toward longer genes but this is not true for down-regulated genes, suggesting MeCP2 may selectively repress long genes. Since genes involved in neuronal connectivity and communication, such as cell adhesion and cell-cell signaling genes, are enriched among longer genes, their misregulation following loss of MeCP2 suggests a possible etiology for altered circuit function in Rett syndrome.