TY - JOUR T1 - Methylation-sensitive expression of a DNA demethylase gene serves as an epigenetic rheostat JF - bioRxiv DO - 10.1101/015941 SP - 015941 AU - Ben P. Williams AU - Daniela Pignatta AU - Steven Henikoff AU - Mary Gehring Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/03/04/015941.abstract N2 - Genomes must balance active suppression of transposable elements (TEs) with the need to maintain gene expression. In Arabidopsis, euchromatic TEs are targeted by RNA-directed DNA methylation (RdDM). Conversely, active DNA demethylation prevents accumulation of methylation at genes proximal to these TEs. It is unknown how a cellular balance between methylation and demethylation activities is achieved. Here we show that both RdDM and DNA demethylation are highly active at a TE proximal to the major DNA demethylase gene ROS1. Unexpectedly, and in contrast to most other genomic targets, expression of ROS1 is promoted by DNA methylation and antagonized by DNA demethylation. We demonstrate that inducing methylation of the ROS1 proximal region is sufficient to restore ROS1 expression in an RdDM mutant. Additionally, methylation-sensitive expression of ROS1 is conserved in other species, suggesting it is adaptive. We propose that the ROS1 locus functions as an epigenetic rheostat, tuning the level of demethylase activity in response to methylation alterations, thus ensuring epigenomic stability.Author Summary Organisms must adapt to dynamic and variable internal and external environments. Maintaining homeostasis in core biological processes is crucial to minimizing the deleterious consequences of environmental fluctuations. Genomes are also dynamic and variable, and must be robust against stresses, including the invasion of genomic parasites, such as transposable elements (TEs). In this work we present the discovery of an epigenetic rheostat in plants that maintains homeostasis in levels of DNA methylation. DNA methylation typically silences transcription of TEs. Because there is positive feedback between existing and de novo DNA methylation, it is critical that methylation is not allowed to spread and potentially silence transcription of genes. To maintain homeostasis, methylation promotes the production of a demethylase enzyme that removes methylation from gene-proximal regions. The demethylation of genes is therefore always maintained in concert with the levels of methylation suppressing TEs. In addition, this DNA demethylating enzyme also represses its own production in a negative feedback loop. Together, these feedback mechanisms shed new light into how the conflict between gene expression and genome defense is maintained in homeostasis. The presence of this rheostat in multiple species suggests it is an evolutionary conserved adaptation. ER -