Methyl-CpG-binding protein 2 represses LINE-1 expression and retrotransposition but not Alu transcription

In order to explore the defense mechanism by which retrotransposons are rep ressed, we assessed the ability of methyl-CpG-binding protein 2, MeCP2, to influence LINE-1 (L1) and Alu transcription and, furthermore, L1 retrotrans position. In transient transfection assays, targeting of the transcriptiona l-repression domain (TRD) of MeCP2 (via a linked Gal4 DNA-binding domain) t o the transcriptional start site of L1 promoter-driven reporter constructs efficiently repressed transcription. The Gal4-linked TRD of the related met hyl-CpG-binding protein MBD1 also repressed transcription but not that of M BD2. Furthermore, full-length MeCP2 effectively repressed transcription of a HpaII-methylated L1 reporter. Secondly, we used a genetic assay employing a full-length neo-marked L1 reporter construct to study L1 retrotransposit ion. We found the Gal4-linked TRD of MeCP2 to repress effectively L1 retrot ransposition when targeted to the retrotransposition reporter. Retrotranspo sition was also reduced in response toin vitro HpaII methylation of the rep orter and was further decreased by co-expressed full-length MeCP2. In strik ing contrast expression of the Gal4-linked TRD of MeCP2 had no inhibiting e ffect on transcription of an AluSx reporter tagged with a 7S-upstream seque nce. Furthermore, full-length MeCP2 abrogated the methylation-induced repre ssion of this reporter. Our results indicate that MeCP2 serves a role in re pression of L1 expression and retrotransposition but has no inhibiting effe ct on Alu transcription.