Developmental Methylome of the Medicinal Plant Catharanthus roseus Unravels the Tissue-Specific Control of the Monoterpene Indole Alkaloid Pathway by DNA Methylation

Abstract

Catharanthus roseus produces a wide spectrum of monoterpene indole alkaloids (MIAs). MIA biosynthesis requires a tightly coordinated pathway involving more than 30 enzymatic steps that are spatio-temporally and environmentally regulated so that some MIAs specifically accumulate in restricted plant parts. The first regulatory layer involves a complex network of transcription factors from the basic Helix Loop Helix (bHLH) or AP2 families. In the present manuscript, we investigated whether an additional epigenetic layer could control the organ-, developmental- and environmental-specificity of MIA accumulation. We used Whole-Genome Bisulfite Sequencing (WGBS) together with RNA-seq to identify differentially methylated and expressed genes among nine samples reflecting different plant organs and experimental conditions. Tissue specific gene expression was associated with specific methylation signatures depending on cytosine contexts and gene parts. Some genes encoding key enzymatic steps from the MIA pathway were found to be simultaneously differentially expressed and methylated in agreement with the corresponding MIA accumulation. In addition, we found that transcription factors were strikingly concerned by DNA methylation variations. Altogether, our integrative analysis supports an epigenetic regulation of specialized metabolisms in plants and more likely targeting transcription factors which in turn may control the expression of enzyme-encoding genes.

Integration of high-throughput omics technologies in medicinal plant research: The new era of natural drug discovery

“…As an example, agronomic trait-associated SNPs identified by pan-genome analysis indicated that location and year significantly affected yield-related phenotypes in pigeon pea ( Cajanus cajan ), a plant species with rich vitamin B, protein, ascorbic acid and carotene ( Zhao et al., 2020 ). Developmental methylome of the medicinal plant Cape periwinkle ( Catharanthus roseus ) determined that cellular and physiological functions are likely to be impacted by tissue-specific covariations between context-dependent DNA methylation ( Dugé de Bernonville et al., 2020 ). The cold environment affected ginsenosides accumulation in perennial American ginseng ( Panax quinquefolium ), and a cyclically reversible dynamism between methylation and demethylation of DNA was also reported in response to temperature seasonality ( Hao et al., 2020 ).…”

Application of metabolic engineering to enhance the content of alkaloids in medicinal plants

“…Catharanthus roseus produces a wide range of terpenoid indole alkaloids which can be divided into monomeric indole alkaloids (serpentine, strictosidine, ajmalicine, serpentine, catharanthine, vindoline, tabersonine, etc) and dimeric indole alkaloids such as vinblastine and vincristine which are derived from the coupling of catharanthine and vindoline ( Dugé de Bernonville et al, 2020 ). These alkaloids are biosynthesized by the condensation of tryptamine (indole moiety) and secologanin (monoterpenoid) by strictosidine synthase to form strictosidine, a common precursor to all terpenoid indole alkaloids ( Peebles et al, 2011 ).…”

Hairy roots: An untapped potential for production of plant products

“…Some genes encoding key enzymatic steps from the TIA pathway were found to be simultaneously differentially expressed and methylated. The transcription factor ORCA2 displayed hypermethylation in two differentially methylated regions (DMRs) which corresponded to a higher expression in roots vs. mature leaves (Duge de Bernonville et al, 2020).…”