Replication and translation of epigenetic information

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Methyl-cytosine binding proteins (MeCPs) play a central role in the mediation of epigenetic effects. They bind to methylated sites in the DNA, recruit histone deacetylases (HDACs9 which may then cause chromatin condensation and transcriptional silencing. We have previously studied the dynamics of DNA replication in living mammalian cells using fluorescence labeling and bleaching techniques. We want to extend this work now to the re-establishment of chromatin structures (duplication of epigenetic information) on the newly synthesized DNA strand and investigate the turn-over and interaction of MeCPs in the postreplicative reassembly of chromatin. These studies should elucidate whether MeCPs bind stably to chromatin or whether they are in constant flux, which would facilitate the dynamic modulation of chromatin states. We have recently observed that the expression level of a member of this family, MeCP2, has a profound effect on the spatial organization of the genome in living cells. We will investigate which functional domains of MeCP2 are involved in this large scale reorganization and whether other family members show similar effects. We will later investigate whether this chromatin reorganisation does also effect gene expression. These studies should help to elucidate how MeCPs mediate and regulate epigenetic effects.