When DNA methylation integrity fails: Lessons from plant aging and tissue culture.

Plants maintain DNA methylation landscapes with high fidelity. Multiple pathways are coordinated to maintain DNA methylation patterns over many millions of cell divisions, reproductive generations and even evolutionary timescales. As DNA methylation maintenance is typically a robust and accurate process, scenarios in which the fidelity of methylation patterns is compromised represent compelling opportunities to gain a deeper understanding of DNA methylation stability. In this review, we discuss recent research that sheds light on two points of failure for DNA methylation maintenance: plant aging and tissue culture. In both cases, loss of DNA methylation is associated with the activation of transposable elements, potentially causing further genetic instability. We propose that uncovering the precise relationship between epigenetic instability, tissue culture, and somaclonal variation is crucial and timely, as epigenetic and genetic instability in tissue culture undermines the core strategy of gene editing to generate new genetic variants with high precision.