Gene body methylation buffers noise in gene expression in plants

Non-genetic variability in gene expression is an inevitable consequence of the stochastic nature of processes driving transcription and translation. While previous studies demonstrated that gene expression noise is negatively correlated with gene body methylation, the function of this correlation remains poorly understood in multicellular systems. Here, we provide a first functional link between gene body methylation and transcription noise in plants. We investigated a mutant with partial loss of CG methylation (met1-1) and 10 epigenetic recombinant inbred lines (epiRILs) generated by a cross between Col-0 and met1-3 plants, and observed an increase in gene expression noise, but this was not the case in met1-3 with complete loss of CG methylation. Loss of CG methylation in met1-3 could be compensated by a low but significant gain of non-CG methylation that buffers the noise in gene expression. Overall, our results show that gene body methylation has a functional role in reducing variability in transcription in a large subset of housekeeping genes, which require precise expression patterns to meet metabolic requirements. Genes lacking this noise-buffering effect are mainly enriched in stress response, where variability in gene expression can be seen as highly beneficial.