Epigenetic “Switch” May Help Breeders Boost Hemp Flavonoids and Cannabinoids, Study Finds

A study in Frontiers in Plant Science reports that “chromatin opening”, a form of epigenetic regulation that helps control whether genes are easy or hard to activate, may play a central role in why some cannabis varieties produce more flavonoids and cannabinoids than others.

Researchers from the China Academy of Chinese Medical Sciences and China Jiliang University analyzed female inflorescences from two industrial hemp cultivars that differed sharply in glandular trichome density, the specialized structures that act as a production and storage site for many secondary metabolites. Using a combined approach that integrated metabolomics, transcriptomics, and ATAC-seq, the team reported pronounced differences between the two cultivars in metabolites, gene expression, and chromatin accessibility.

In total, the researchers identified 491 differentially accumulated metabolites, 8,343 differentially expressed genes, and 11,376 genes associated with changes in chromatin accessibility between the cultivars. The paper describes the work as a way to better define the “epigenetic regulatory network underlying secondary metabolite biosynthesis,” which it notes remains “poorly understood in hemp.”

One of the clearest signals involved flavonoids. The team reported that increased chromatin accessibility at the promoters of multiple flavonoid-biosynthetic genes “up-regulated their expression,” which corresponded with higher flavonoid accumulation in the high-trichome cultivar. The dataset highlighted examples of flavonoid differences between varieties, including higher levels of compounds such as kaempferol in the high-trichome cultivar.

Cannabinoid differences appeared more complicated. While the study found that promoter accessibility in cannabinoid-related genes can influence content, it concluded that the key driver behind cannabinoid divergence was tied more to upstream processes than direct “on/off” control of the core cannabinoid pathway. Specifically, the paper points to differential chromatin accessibility involving fatty acid biosynthesis and genes connected to trichome density, including trichome initiation, methyl jasmonate (MeJA) signaling, and the identity of floral organs.

Put simply, the researchers suggest the higher-cannabinoid cultivar may be benefiting from a stronger supply chain: more precursor production, more trichomes to manufacture and store metabolites, and epigenetic changes that make those supporting systems easier to activate. The study frames this as a “chromatin opening – transcription – metabolism” model for understanding how industrial hemp’s biochemical profile is shaped.

The authors say the findings could help breeders by providing “efficient and precise molecular markers” to support selection and development of new Cannabis varieties with tailored cannabinoid and flavonoid profiles.

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