Methylation dynamics during the maternal-to-zygotic genome transition in dioecious species

The starting point of a new generation in sexually reproducing species is fertilization. In many species, fertilization is followed by cell divisions controlled primarily by maternal transcripts, with little to no zygotic transcription. The activation of the zygotic genome (ZGA) is part of a process called maternal-to-zygotic transition (MZT), during which transcripts from the zygotic genome take control of development, setting the conditions for cellular specialization. While we know that epigenetic processes (e.g. methylation) are involved in the MZT, their roles and interplay in the transition are largely unknown. I developed a model and used simulations to elucidate the interaction between possible epigenetic processes, namely methylation processes, involved in the MZT. The model focuses on the dynamics of global methylation levels and how these interact with factors such as a parental repressor and the nucleocytoplasmic ratio to trigger the ZGA, followed by development from fertilization to adulthood. In addition, I included transgenerational effects transmitted to the zygote from both parents through their gametes to show that these may set the stage for plastic developmental processes. I demonstrate that the rates of maintenance methylation and demethylation, which are important for the achievement of the final methylation levels of an individual, exhibit a certain level of flexibility in terms of parameter values. I find that high final methylation levels require more restricted combinations of parameter values. The model is discussed in the context of the current empirical knowledge and provide suggestions for directions of future empirical and theoretical studies.


Methylation dynamics (Heaviside model)
This model assumes that alpha=1.0, beta=0.0, delta=0.0 and zeta=0.0 before ZGA. As a consequence, hemimethylated sites are transitional and will be turned into homomethylated sites because of alpha=1.0.

Plot 1
This plot shows the comparison of cell division dynamics between a simulation with a maternal repressor speeding up cell divisions and a simulation with constant intrinsic cell division rate. Vertical bars mark the cell division at which the number of cells reach the specified equilibrium.

Plot 2
This plot shows the change in maternal repressor across cell divisions (rho) and the consequent change in cell division speed (mu).

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Plot 3
This plot shows the methylation dynamics during the first generation, in which the initial proportion of homomethylated sites reach an equilibrium marked by the vertical bars.

Plot 5
This plot shows the methylation dynamics across ngen generations in males.

Plot 6
This plot shows the methylation dynamics across ngen generations in females.

Plot 10
This plot shows the values of X that can result from a given value of alpha, beta or delta.

Plots 11
These plots show the combinations of values of alpha, beta and delta that yield the specified values of X.

Plot 12
This plot shows the ranges of alpha, beta and delta that can result in different values of X.

Plot 13
This plot shows the number of cell divisions after ZGA that are necessary to reach a specific X for different values of alpha, beta and delta, starting from a specific X0.

Plot 15
This plot shows the number of cell divisions after ZGA that are necessary to reach the equilibrium X, for specific values of alpha, beta and delta, starting from different initial values of X0.

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