Methyl-seq, ATAC-seq, and Hi-C of Timema cristinae

Gene body methylation is one of the most taxonomically widespread epigenetic marks, yet its function and evolutionary history are poorly understood. While there is a positive association between gene body methylation and gene expression in many organisms, the mechanisms behind this relationship are unclear. Here, we investigate the function of gene body methylation in the stick insect Timema cristinae. We compare patterns of genome-wide gene body methylation to gene expression, open chromatin peaks, and chromatin compartments. We find that 95% of genes with gene body methylation occur in open chromatin compartments (euchromatin). Furthermore, highly expressed genes are impoverished in methylation at their transcription start site (TSS), which is associated with a peak of open chromatin. These findings suggest that the positive correlation between gene body methylation and gene expression is due to chromatin compartment structure. Yet, methylation around the TSS is associated with gene expression, possibly playing an inhibitory role as in vertebrates. Lastly, comparative analysis of Apis mellifera reveals a similar relationship between methylation and chromatin compartments, but not gene expression. These results suggest a possible explanation for the heterogeneous association between gene body methylation and gene expression and give insight into DNA methylations role in regulating gene expression.