Methyl CpG Binding Protein 2 (MeCP2) is a key transcriptional regulator in the brain [1]. MECP2 mutations and expression deficits result in a broad range of neurodevelopmental disorders, including Rett syndrome (RTT) and autism spectrum disorders [2,3]. In mice (Mecp2) and humans (MECP2), alternative splicing of a single gene leads to the generation of two protein isoforms MeCP2E1 and MeCP2E2 (mature transcripts for Mecp2e1 and Mecp2e2 are shown in Figure 1A) [4,5]. We and others have shown differential expression of the two Mecp2/MeCP2 isoforms in mouse brain [5-7]. Recent studies suggest that MeCP2E1 is the most relevant isoform for RTT pathology [8,9]. Moreover, overexpression of Mecp2e2, but not Mecp2e1, promotes neuronal cell death [10], implicating the importance of proper regulation of both Mecp2 isoforms in the brain.
