By investigating the role of DNA methylation enzymes in basal plants, we discovered the potential of a particular enzyme to trigger methylation in gene bodies (Yaari et al., 2019). Our data also propose a new paradigm for the establishment of gene body methylation in flowering plants (Yaari et al., 2019). Finally, by identifying the molecular mechanism of novel methylation enzymes, we can now artificially manipulate gene body methylation to our own needs.
By investigating the dynamics of gene body methylation in honey bees, an organism that mediates methylation specifically to gene bodies, we discovered that genic methylation globally fluctuates during honey bee development (Harris et al., 2019). However, these changes cause no gene expression alterations. Intriguingly, despite the global alterations, tissue-specific methylation patterns of complete genes or exons are rare, implying robust maintenance of genic methylation during development. Additionally, we show that methylation maintenance fluctuates in somatic cells, while reaching maximum fidelity in sperm cells. Based on these results, we propose that gene body methylation can oscillate during development if it is kept to a level adequate to preserve function. Additionally, our data suggest that heightened genic methylation at CH sites (N=A, C or T) is a conserved regulator of animal nervous systems.
By collaborating with the Gideon Grafi’s group, we identified in the model plant, Arabidopsis thaliana, a transcriptional feedback loop between two methylation enzymes, which is based on a genic methylation of one of the methylases (Yadav et al., 2018).
By collaborating with Danny Chamovitz’s and Tamir Tuller’s groups, we identified a novel nuclear factor, COP9 signalosome, that its disruption alters DNA methylation particularly within genic regions (Tuller et al., 2018).
By manipulating the level of different methylation contexts in moss, we managed to create a plant that has comparable level of CG and non-CG methylation. We used this plants to investigate the transcriptional roles of the particular methylation contexts. This study which have been submitted for publication (Domb et al., 2020) shows that non-CG methylation is a stringer silencer than the canonical CG methylation. This result explain the development of non-CG methylation in plants and the ambient transcriptional role of CG methylation in genes.
We have developed a computational bioinformatic tool to analyze methylome NGS data in a single read resolution. We used this tool to reveal methylation processivity and stochasticity patterns of DNA methylases. Intriguingly, our data suggest that methylation in genes and TEs is processive and stochastic, respectively. This result implies on the biological regulation of these elements during development.
