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Epigenetic inheritance of gene silencing is maintained by a self-tuning mechanism based on resource competition.

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Karin, Omer 
Miska, Eric A 
Simons, Benjamin D 


Biological systems can maintain memories over long timescales, with examples including memories in the brain and immune system. It is unknown how functional properties of memory systems, such as memory persistence, can be established by biological circuits. To address this question, we focus on transgenerational epigenetic inheritance in Caenorhabditis elegans. In response to a trigger, worms silence a target gene for multiple generations, resisting strong dilution due to growth and reproduction. Silencing may also be maintained indefinitely upon selection according to silencing levels. We show that these properties imply the fine-tuning of biochemical rates in which the silencing system is positioned near the transition to bistability. We demonstrate that this behavior is consistent with a generic mechanism based on competition for synthesis resources, which leads to self-organization around a critical state with broad silencing timescales. The theory makes distinct predictions and offers insights into the design principles of long-term memory systems.



biological memory, design principles, dynamical systems, epigenetic memory, mathematical modeling, self organization, self-tuning to criticality, small RNAs, systems biology, transgenerational inheritance, Animals, Epigenesis, Genetic, Gene Silencing, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Inheritance Patterns

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Cell Syst

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Elsevier BV
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Wellcome Trust (098357/Z/12/Z)
Wellcome Trust (219478/Z/19/Z)
Medical Research Council (MC_PC_17230)