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Fundamental principles and destabilizing noise sources for epigenetic memory

Characterize the fundamental principles that govern faithful inheritance of transcriptional information in read–write histone modification systems and determine which stochastic noise sources (such as enzymatic reaction noise versus replication-induced histone mark dilution) destabilize bistable epigenetic states.

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Background

Previous models of epigenetic inheritance often rely on stochastic simulations, which makes it difficult to extract general organizing principles or to attribute instability to particular noise sources.

A clear theoretical understanding of which mechanisms ensure faithful inheritance, and which sources of noise compromise it, would enable predictive control of epigenetic memory stability.

References

However, these works were heavily based on numerical simulations of stochastic systems and, beyond the read-write feedback and the appearance of bistable behaviour, it has been unclear, in general, what fundamental principles govern the faithful inheritance of transcriptional information and which sources of noise could destabilise it.

— Theory of epigenetic switching due to stochastic histone mark loss during DNA replication (2407.06019 - Miangolarra et al., 8 Jul 2024) in Introduction