Abstract
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.
Highlights
How can the fusion of two highly specialized cells generate a state of totipotency, from which all other cell types descend? It is known that the genome of a cell at any time point is only partially activated, with the majority of genes being tightly regulated by highly specialized mechanisms [1]
Based on the current empirical knowledge, I propose a model for the dynamics of the intra- and transgenerational epigenetic remodeling of global methylation levels in particular that occur during the transition from a totipotent zygote into the highly specialized epigenetic patterns of the gametes in the adult germline
Because methylation dynamics across loci are highly variable, global methylation levels seem to be a reasonable simplification for defining cell types
Summary
How can the fusion of two highly specialized cells (sperm and egg) generate a state of totipotency, from which all other cell types descend? It is known that the genome of a cell at any time point is only partially activated, with the majority of genes being tightly regulated by highly specialized mechanisms [1]. While mechanisms such as mRNA targeting by small RNAs [2] and protein modification [3] regulate gene expression at the post-transcriptional level, epigenetic mechanisms such as DNA methylation [4] and chromatin modifications [5] are involved in the pretranscriptional control of gene expression. These mechanisms are important during the initial stages of development right after fertilization, when the parental genomes need to function together and synchronize their genes in order to create a viable individual [6]. Based on the current empirical knowledge, I propose a model for the dynamics of the intra- and transgenerational epigenetic remodeling of global methylation levels in particular that occur during the transition from a totipotent zygote into the highly specialized epigenetic patterns of the gametes in the adult germline
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