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EpiSys - Experimental and theoretical methods for dissecting the dynamics of epigenetic gene silencing in living cells


EpiSys is an interdisciplinary research consortium for studying the regulatory networks of epigenetic gene silencing in mammalian cells. The project is part of the BMBF SysTec program on new methods in systems biology. Epigenetics is being recognized as pivotal to numerous fields of medical research including cancer, developmental diseases and the reprogramming of adult somatic cells into stem cells. Although it has moved to the forefront of human genetics research only recently, epigenetic mechanisms are already being exploited for disease diagnosis and treatments. A new generation of anti-cancer drugs bears witness to this rapid progress. However, such drugs affect epigenetic modifications in the genome in complex and poorly understood ways. Thus, there is an urgent need for predictive models of epigenetic regulatory networks. In EpiSys new methods for visualizing, quantifying and perturbing the dynamics of these networks in living cells, together with mathematical analysis and modeling approaches are being developed and applied to studies of epigenetic gene silencing.

Regulatory epigenetic network mediating the transition between a biologically inactive heterochromatin state and an open euchromatin conformation competent for transcription. For example, histone methylations such as H3K9me2/3 through Suv3-9h and the recruitment of heterochromatin protein 1 (HP1) can cooperate in gene silencing, whereas demethylation by Jmjd2 or H3K4 methylation participate in chromatin opening. Color code: red, chromatin-modifying enzymatic activities; blue, core/linker histones, with their posttranslationally methylated (me), acetylated (ac) and phosphorylated (pho) states at the indicated lysine residues; green, nucleic acids; yellow, structural chromatin components. The solid black lines symbolize association between proteins, while the dashed lines indicate inhibition of interactions.

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