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ORIGINAL RESEARCH article

Front. Plant Sci.

Sec. Plant Metabolism and Chemodiversity

This article is part of the Research TopicMolecular Mechanisms and Multi-Omics Approaches in Plant Secondary Metabolism: Regulation, Stress Responses, and Biotechnological ApplicationsView all 12 articles

Chromatin accessibility directly governs flavonoid biosynthesis and indirectly orchestrates cannabinoid production in Cannabis

Provisionally accepted
Yuanchang  MaYuanchang Ma1Xiuye  WeiXiuye Wei2,3Weixin  ZhouWeixin Zhou1An  XieAn Xie1Yongzhong  ChenYongzhong Chen1Chen  YangChen Yang1Lingcheng  ChenLingcheng Chen1Linlin  DongLinlin Dong3*Kang  NingKang Ning1,3*
  • 1China Jiliang University, Hangzhou, China
  • 2Chengdu University of Traditional Chinese Medicine, Chengdu, China
  • 3China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica, Beijing, China

The final, formatted version of the article will be published soon.

Secondary metabolites in hemp enhance its pharmaceutical and nutraceutical value, yet the epigenetic regulatory network underlying secondary metabolite biosynthesis remains poorly understood in hemp. Here, we profiled the inflorescences of two cultivars with different trichome density by integrating metabolomics, transcriptomics and ATAC-seq. Multi-omics data revealed pronounced differences in metabolites (491 differentially accumulated metabolites (DAMs)), transcripts (8343 differentially expressed genes (DEGs)), and chromatin accessibility (11376 different accessibility genes, (DAGs)) between two cultivars. Integrated analyses reveal that increased chromatin accessibility at the promoters of several flavonoid-biosynthetic genes up-regulated their expression, resulting in the accumulation of flavonoids. Although chromatin accessibility of cannabinoid biosynthetic gene promoters modulates content, differential chromatin accessibility of the promoter of fatty acid biosynthetic and trichome density (trichome initiation, MeJA signaling, and identity of floral organ) related genes constitutes the key driver underlying cannabinoid divergence between two cultivars. Our study advances the understanding of epigenetic regulation of plant secondary metabolites and offers a novel strategy for enhancing cannabinoid and flavonoid content in Cannabis, providing efficient and precise molecular markers for the selection and breeding of new cannabis varieties.

Keywords: Cannabis, chromatin accessibility, secondary metabolites, Cannabinoids, Flavonoid

Received: 18 Aug 2025; Accepted: 08 Dec 2025.

Copyright: © 2025 Ma, Wei, Zhou, Xie, Chen, Yang, Chen, Dong and Ning. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Linlin Dong
Kang Ning

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