Antagonistic histone post-translational modifications improve the fidelity of epigenetic inheritance - a Bayesian perspective

Building on our previous study which proposed mechanisms for maintaining fidelity by utilizing only half the parental nucleosomes, the current work considers the effect of an additional antagonistic PTM sequence. We represent the joint PTM sequence by an appropriate Markov model and the DNA replication fork as a noisy communication channel. An optimal Bayesian sequence estimator is then employed at each of the daughter chromatids to reconstruct the primary PTM pattern. A high-fidelity reconstruction, potentially aided by the enzyme machinery, is shown to be possible in the presence of epigenetic memory. The structural properties derived for the optimal estimator are then verified through simulations, which show the improvement in fidelity of inheritance with antagonism. This is further supported empirically through observations from some recent experimental data CONCLUSIONS: Our work provides a computational model to quantify the effect of combinatorial histone PTMs in epigenetic inheritance. The fidelity of reconstruction of the primary histone PTM post-replication, is shown to be enhanced in the presence of antagonistic PTMs in the vicinity.