5-Azacytidine increases tanshinone production in Salvia miltiorrhiza hairy roots through epigenetic modulation

Abstract

Recent studies have indicated strong connections between epigenetic modulation and secondary metabolites in plants. It is vital to understand the roles of epigenetics in the production of secondary metabolites. In this study, the inhibitor of DNA methylation 5-azacytidine (5-Az) was used on the hairy roots of the medicinal plant Salvia miltiorrhiza to investigate its effect on secondary metabolite production, gene expression, methylation levels in genomic DNA and promoter regions. Our results showed that the contents of tanshinones in S. miltiorrhiza hairy roots increased by 1.5–5 times, and some genes in the biosynthesis pathway showed an upward trend. According to our NGS analysis, the methylation pattern in the promotor of the gene encoding copalyl diphosphate synthase (CPS) was altered, and 51 out of 145 cytosines were demethylated during 5-Az treatment. A total of 36 putative transcription factors (TFs) binding cites were identified in these demethylation sites. Among these TFs binding cites, cis-regulatory elements for the binding of NF-Y and MYB were frequently found in our results. This is the first report to demonstrate a possible mechanism of DNA methylation participating in tanshinone biosynthesis in S. miltiorrhiza hairy roots by modulating the CPS promoter and TFs binding sites.

The Smi-miR858a-SmMYB module regulates tanshinone and phenolic acid biosynthesis in Salvia miltiorrhiza

“…Smi-miR5072 may participate in terpenoid backbone biosynthesis through regulating the enzyme gene acetyl-CoA C-acetyltransferase gene ( SmAACT ) [ 40 ]. Smi-miR7972 plays a role in tanshinone biosynthesis through regulating DEMETER-like DNA glycosylase 1 ( SmDML1 ), a gene associated with DNA methylation and demethylation in S. miltiorrhiza [ 54 , 58 ]. Smi-miR319, Smi-miR159, and Smi-miR828 regulate anthocyanin and phenolic acid biosynthesis through targeting a subset of SmMYB genes [ 12 ].…”

The Sink-Source Relationship in Cucumber (Cucumis sativus L.) Is Modulated by DNA Methylation

“…However, high concentrations of methylation inhibitors can lead to the yellowing and even death of plant organs [ 54 , 55 , 56 ]. Previous studies have shown that DNA methylation inhibitors in a certain concentration range can change DNA methylation levels and promote gene expression after treating rice, Arabidopsis , Salvia miltiorrhiza and strawberry [ 57 , 58 , 59 , 60 ]. In this study, four concentrations of 5-Aza-dC, 5 μM, 10 μM, 20 μM and 30 μM, were tested in a pretest study according to previous studies [ 61 , 62 ], and 20 μM of 5-Aza-dC was selected for treatment.…”

Dynamic DNA Methylation Regulates Season-Dependent Secondary Metabolism in the New Shoots of Tea Plants

“…In plants such as medicinal plants, the production of secondary metabolites was found to be closely associated with 5mC methylation. 45 In tea plants, it had been reported that 5mC methylation involved in chilling response, 18 albino type, 46 ABA and indole accumulation in postharvest processing. 47,48 These studies implied that 5mC methylation plays an important role in stress response before and after harvest of tea and is involved in formation of tea quality.…”