Histone deacetylases repress the accumulation of licochalcone A by inhibiting the expression of flavonoid biosynthetic pathway-related genes in licorice (Glycyrrhiza inflata)

Histone deacetylases (HDACs) play a crucial role in regulating plant growth, stress responses, and specialized metabolism. Licorice, utilized as both food and herbal medicine for millennia, includes Glycyrrhiza inflata as one of its primary medicinal species used globally. This study investigated the regulatory function of HDAC-mediated histone deacetylation in flavonoid biosynthesis in licorice. The research identified nineteen HDACs in the G. inflata genome. Abiotic stresses and plant hormones were found to influence flavonoid compound accumulation, correlating with altered expression patterns of HDAC genes and global histone H3 acetylation (H3ac) levels. Notably, several HDAC inhibitors enhanced flavonoid accumulation in G. inflata. Subsequent RNA-seq analysis revealed that the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) activated the expression of multiple genes related to flavonoid biosynthesis. ChIP-qPCR demonstrated that SAHA treatment increased the H3ac levels of flavonoid synthesis-related genes. Furthermore, overexpression of GiHDA2b, an HDAC member, decreased, while RNAi of GiHDA2b increased, the levels of expression and H3K18 acetylation of licochalcone A (LCA) biosynthetic genes indicating its negative role in flavonoid biosynthesis. This research provides valuable insights into the regulatory roles of GiHDACs and histone deacetylation in flavonoid biosynthesis in licorice, potentially contributing to improved bioactive compound production in medicinal plants.