Maximum DNA Methylation Fidelity in the Germline Tolerates Global Non-Functional Gene Body Methylation Dynamics During Development

Abstract

Although active genes frequently exhibit cytosine DNA methylation in animals and plants, the biological function of such methylation remains elusive. 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. Based on these results, we propose that gene body CGmethylation can oscillate in organisms as long as it is being kept to an adequate level to preserve its function during development and its pattern across generations. Unlike CG-methylation, we discovered a non-CG methylation signal in bee heads that resembles the one found in mammalian brain tissue, suggesting that heightened non-CG methylation is a conserved regulator of animal nervous systems.