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High fidelity epigenetic inheritance: Information theoretic model predicts threshold filling of histone modifications post replication
Authors:Nithya Ramakrishnan  Sibi Raj B Pillai  Ranjith Padinhateeri
Institution:1. Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India ; 2. Department of Electrical Engineering, Indian Institute of Technology Bombay, Mumbai, India ; University of Essex, UNITED KINGDOM
Abstract:During cell devision, maintaining the epigenetic information encoded in histone modification patterns is crucial for survival and identity of cells. The faithful inheritance of the histone marks from the parental to the daughter strands is a puzzle, given that each strand gets only half of the parental nucleosomes. Mapping DNA replication and reconstruction of modifications to equivalent problems in communication of information, we ask how well enzymes can recover the parental modifications, if they were ideal computing machines. Studying a parameter regime where realistic enzymes can function, our analysis predicts that enzymes may implement a critical threshold filling algorithm which fills unmodified regions of length at most k. This algorithm, motivated from communication theory, is derived from the maximum à posteriori probability (MAP) decoding which identifies the most probable modification sequence based on available observations. Simulations using our method produce modification patterns similar to what has been observed in recent experiments. We also show that our results can be naturally extended to explain inheritance of spatially distinct antagonistic modifications.
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