MeCP2, a protein that binds to methylated CpG dinucleotides, plays a key role in linking DNA methylation to histone methylation. This study shows that MeCP2 associates with histone methyltransferase activity in vivo, specifically targeting lysine 9 of histone H3. Two domains of MeCP2 are involved in this interaction. The study also demonstrates that MeCP2 facilitates H3 lysine 9 methylation in the H19 gene, a gene it represses. These findings suggest that MeCP2 acts as a bridge between DNA methylation and histone methylation, reinforcing a repressive chromatin state. This mechanism may be essential for maintaining and transmitting the repressive state of imprinted promoters. The study also shows that MeCP2 can recruit histone deacetylase activity, which contributes to gene silencing. However, the full repressive potential of MeCP2 may involve additional mechanisms, such as histone methylation. The results indicate that MeCP2 is involved in a self-reinforcing cycle of repression, where histone methylation may promote further DNA methylation, helping to maintain the repressed state. The study provides evidence that MeCP2 connects DNA methylation to histone methylation, reinforcing the repressive function of these two modifications.MeCP2, a protein that binds to methylated CpG dinucleotides, plays a key role in linking DNA methylation to histone methylation. This study shows that MeCP2 associates with histone methyltransferase activity in vivo, specifically targeting lysine 9 of histone H3. Two domains of MeCP2 are involved in this interaction. The study also demonstrates that MeCP2 facilitates H3 lysine 9 methylation in the H19 gene, a gene it represses. These findings suggest that MeCP2 acts as a bridge between DNA methylation and histone methylation, reinforcing a repressive chromatin state. This mechanism may be essential for maintaining and transmitting the repressive state of imprinted promoters. The study also shows that MeCP2 can recruit histone deacetylase activity, which contributes to gene silencing. However, the full repressive potential of MeCP2 may involve additional mechanisms, such as histone methylation. The results indicate that MeCP2 is involved in a self-reinforcing cycle of repression, where histone methylation may promote further DNA methylation, helping to maintain the repressed state. The study provides evidence that MeCP2 connects DNA methylation to histone methylation, reinforcing the repressive function of these two modifications.