DNA methylation of active genes, also known as gene body methylation, is found in many animal and plant genomes. Despite this, the transcriptional and developmental role of such methylation remains poorly understood. Here, we explore the dynamic range of DNA methylation in honey bee, a model organism for gene body methylation.

Our data show that CG methylation in gene bodies globally fluctuates during honey bee development. However, these changes cause no gene expression alterations. Intriguingly, despite the global alterations, tissue-specific CG methylation patterns of complete genes or exons are rare, implying robust maintenance of genic methylation during development. Additionally, we show that CG methylation maintenance fluctuates in somatic cells, while reaching maximum fidelity in sperm cells. Finally, unlike universally present CG methylation, we discovered non-CG methylation specifically in bee heads that resembles such methylation in mammalian brain tissue.

Based on these results, we propose that gene body CG methylation can oscillate during development if it is kept to a level adequate to preserve function. Additionally, our data suggest that heightened non-CG methylation is a conserved regulator of animal nervous systems.