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 (HDACs), which may then cause chromatin condensation and transcriptional silencing. Here, we want to investigate the re-establishment of chromatin structures (duplication of epigenetic information) on the newly synthesized DNA after replication and repair of DNA damage. Moreover, we will determine the turnover and interaction of MeCPs with chromatin, compare it with other chromatin factors and test its dependency and impact on DNA and histone modifications. We have recently reported that the expression level of MeCP2 and other MBDs, has a profound effect on the spatial organization of the genome in living cells and changes throughout differentiation. This effect is mediated by the MBD and Rett patient mutations reduce the ability of MeCP2 to reorganize chromatin. We will investigate whether this chromatin reorganization plays a role in the loss of pluripotency and/or the stability of the differentiated state. Finally, we will analyze whether interaction of MeCPs with other proteins, e.g., heterochromatin binding proteins, promotes heterochromatin aggregation and the formation of silencing compartments during differentiation. These studies should help elucidating how MeCPs mediate and regulate epigenetic effects.

M. Cristina Cardoso, PhD
Technische Universität Darmstadt
Building B203 2nd floor
Schnittspahnstr. 10
64287 Darmstadt, Germany

Phone: +49-6151-162377
Fax: +49-6151-162375

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