Abstract
DNA methylation is an indispensable epigenetic modification that dynamically regulates gene expression and genome stability during cell growth and development processes. The target of rapamycin (TOR) has emerged as a central regulator to regulate many fundamental cellular metabolic processes from protein synthesis to autophagy in all eukaryotic species. However, little is known about the functions of TOR in DNA methylation. In this study, the synergistic growth inhibition of Arabidopsis seedlings can be observed when DNA methylation inhibitor azacitidine was combined with TOR inhibitors. Global DNA methylation level was evaluated using whole-genome bisulfite sequencing (WGBS) under TOR inhibition. Hypomethylation level of whole genome DNA was observed in AZD-8055 (AZD), rapamycin (RAP) and AZD + RAP treated Arabidopsis seedlings. Based on functional annotation and KEGG pathway analysis of differentially methylated genes (DMGs), most of DMGs were enriched in carbon metabolism, biosynthesis of amino acids and other metabolic processes. Importantly, the suppression of TOR caused the change in DNA methylation of the genes associated with plant hormone signal transduction, indicating that TOR played an important role in modulating phytohormone signals in Arabidopsis. These observations are expected to shed light on the novel functions of TOR in DNA methylation and provide some new insights into how TOR regulates genome DNA methylation to control plant growth.
Highlights
DNA methylation is an important part of epigenetics, which is widely distributed in microbes, animals and plants
Azacitidine is a specific inhibitor of DNA methylation, which interacts with DNA methyltransferase to inhibit DNA methylation in mammalian (Christman, 2002)
We found that inhibition of target of rapamycin (TOR) reduced whole-genome methylation levels whereas the methylation level of CHH site in the promoter region was increased
Summary
DNA methylation is an important part of epigenetics, which is widely distributed in microbes, animals and plants. DNA methylation plays an important role in controlling transcriptional silencing of transposon, regulating gene expression and maintaining plant development (Moore et al, 2013; Bouyer et al, 2017; Zhang et al, 2018), which is one of the most studied epigenetic modifications in epigenetics. DNA methylation regions are mainly found in highly repetitive sequences (transposon and rDNA), promoter region (suppressing gene expression), coding sequence region and intergenic region. More than 5% of the expressed genes have DNA methylation in their promoter region, and more than 33% of genes contain DNA methylation within the coding sequence region in Arabidopsis (Zhang et al, 2006). Promoter-methylated genes are low expressed and show a greater degree of tissue specific expression, whereas genes methylated in transcribed regions are highly expressed (Zhang et al, 2006). Recently study showed that methylation in transcribed regions can negatively regulate the gene expression (Long et al, 2014; Lou et al, 2014)
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