Caenorhabditis Elegans as a Model for Environmental Epigenetics

The burgeoning field of environmental epigenetics has revealed the malleability of the epigenome and uncovered numerous instances of its sensitivity to environmental influences; however, pinpointing specific mechanisms that tie together environmental triggers, epigenetic pathways, and organismal responses has proven difficult. This article describes how Caenorhabditis elegans can fill this gap, serving as a useful model for the discovery of molecular epigenetic mechanisms that are conserved in humans.

Recent results show that environmental stressors such as methylmercury, arsenite, starvation, heat, bacterial infection, and mitochondrial inhibitors can all have profound effects on the epigenome, with some insults showing epigenetic and organismal effects for multiple generations. In some cases, the pathways connecting the stressor to epigenetic pathways and organismal responses have been elucidated. For example, a small RNA from the bacterial pathogen Pseudomonas aeruginosa induces transgenerational learned avoidance by activating the RNA interference PIWI-interacting RNA pathways across generations to downregulate, via Cer1 retrotransposon particles and histone methylation, maco-1, a gene that functions in sensory neurons to regulate chemotaxis. Mitochondrial inhibitors seem to have a profound effect on both the DNA methylation mark 6mA and histone methylation, and may act within mitochondrial DNA (mtDNA) to regulate mitochondrial stress response genes. Transgenerational transcriptional responses to alcohol have also been worked out at the single-nucleus resolution in C. elegans, demonstrating its utility when combined with modern sequencing technologies. These recent studies highlight how C. elegans can serve as a bridge between biochemical in vitro experiments and the more associative findings of epidemiological studies in humans to unveil possible mechanisms of environmental influence on the epigenome. The nematode is particularly well-suited to transgenerational experiments thanks to its rapid generation time and ability to self-fertilize. These studies have revealed connections between the various epigenetic mechanisms, and so studies in C. elegans that take advantage of recent advancements in sequencing technologies, including single-cell techniques, to gain unprecedented resolution of the whole epigenome across development and generations will be critical.