Analytical treatment of combined replication and biochemical noise in epigenetic switching

Develop an analytical framework that jointly incorporates replication-induced dilution of histone modifications during DNA replication and intrinsic biochemical reaction noise to quantify their combined, potentially synergistic, effects on epigenetic switching rates and memory stability.

Background

Two major noise sources affect epigenetic inheritance: stochastic dilution of histone marks at DNA replication and intrinsic noise in read/write biochemical reactions. While prior analyses have treated these sources separately, their joint impact has not been developed analytically.

Because the combined effects may be synergistic rather than additive, an analytical framework capturing both is needed to accurately predict switching rates and guide experiments.

References

In Refs. the effects of biochemical noise have been examined, but the combination of the two sources of noise in epigenetic systems remains unexplored analytically. Given that their combined effects can be synergistic (rather than additive), further analysis of both sources of noise together will be an important avenue for future research.

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