Publications - Published papers

Please find below publications of our group. Currently, we list 53 papers. Some of the publications are in collaboration with the group of Peter Stadler and are also listed in the publication list for his group. Access to published papers (access) is restricted to our local network and chosen collaborators.
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Chromatin Computation: Epigenetic Inheritance as a Pattern Reconstruction Problem

Christian Arnold, Peter F. Stadler, Sonja J. Prohaska

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Journal of Theoretical Biology 336:61–74 (2013)

Abstract


Eukaryotic histones carry a diverse set of specific chemical modifications that accumulate over the life-time of a cell and have a crucial impact on the cell state in general and the transcriptional program in particular. Replication constitutes a dramatic disruption of the chromatin states that e ectively amounts to partial erasure of stored information. To preserve its epigenetic state the cell reconstructs (at least part of) the histone modifications by means of processes that are still very poorly understood. A plausible hypothesis is that the di erent combinations of reader and writer domains in histone-modifying enzymes implement local rewriting rules that are capable of “recomputing” the desired parental modification patterns on the basis of the partial information contained in that half of the nucleosomes that predate replication.
To test whether such a mechanism is theoretically feasible, we have developed a flexible stochastic simulation system (available at http://www.bioinf.uni-leipzig.de/Software/StoChDyn) for studying the dynamics of histone modification states. The implementation is based on Gillespie’s approach, i.e., it models the master equation of a detailed chemical model. It is ecient enough to use an evolutionary algorithm to find patterns across multiple cell divisions with high accuracy.
We found that it is easy to evolve a system of enzymes that can maintain a particular chromatin state roughly stable, even without explicit boundary elements separating di erentially modified chromatin domains. However, the success of this task depends on several previously unanticipated factors, such as the length of the initial state, the specific pattern that should be maintained, the time between replications, and chemical parameters such as enzymatic binding and dissociation rates. All these factors also influence the accumulation of errors in the wake of cell divisions.

Keywords


chromatin complexity, Gillespie algorithm, evolutionary algorithm, epigenetic inheritance, histone modifications, chromatin computation