Pharmacy College, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Planta. 2023 Sep 5;258(4):74. doi: 10.1007/s00425-023-04223-y.
The hierarchical architecture of chromatins affects the gene expression level of glandular secreting trichomes and the artemisinin biosynthetic pathway-related genes, consequently bringing on huge differences in the content of artemisinin and its derivatives of A. annua. The plant of traditional Chinese medicine "Qinghao" is called Artemisia annua L. in Chinese Pharmacopoeia. High content and the total amount of artemisinin is the main goal of A. annua breeding, nevertheless, the change of chromatin organization during the artemisinin synthesis process has not been discovered yet. This study intended to find the roles of chromatin structure in the production of artemisinin through bioinformatics and experimental validation. Chromosome conformation capture analysis was used to scrutinize the interactions among chromosomes and categorize various scales of chromatin during artemisinin synthesis in A. annua. To confirm the effect of the changes in chromatin structure, Hi-C and RNA-sequencing were performed on two different strains to find the correlation between chromatin structure and gene expression levels on artemisinin synthesis progress and regulation. Our results revealed that the frequency of intra-chromosomal interactions was higher in the inter-chromosomal interactions between the root and leaves on a high artemisinin production strain (HAP) compared to a low artemisinin production strain (LAP). We found that compartmental transition was connected with interactions among different chromatins. Interestingly, glandular secreting trichomes (GSTs) and the artemisinin biosynthetic pathway (ABP) related genes were enriched in the areas which have the compartmental transition, reflecting the regulation of artemisinin synthesis. Topologically associated domain boundaries were associated with various distributions of genes and expression levels. Genes associated with ABP and GST in the adjacent loop were highly expressed, suggesting that epigenetic regulation plays an important role during artemisinin synthesis and glandular secreting trichomes production process. Chromatin structure could show an important status in the mechanisms of artemisinin synthesis process in A. annua.
染色质的层次结构影响腺毛分泌型腺体的基因表达水平和青蒿素生物合成途径相关基因，导致青蒿素及其衍生物在青蒿中的含量存在巨大差异。中国药典中的传统中药“青蒿”被称为黄花蒿 L.。高含量和青蒿素总量是培育青蒿的主要目标，但在青蒿素合成过程中染色质组织的变化尚未被发现。本研究旨在通过生物信息学和实验验证来探索染色质结构在青蒿素生产中的作用。染色质构象捕获分析用于研究青蒿素合成过程中染色体之间的相互作用，并对不同尺度的染色质进行分类。为了确认染色质结构变化的影响，对两个不同的菌株进行了 Hi-C 和 RNA-seq 实验，以找到染色质结构与基因表达水平在青蒿素合成过程中的调控之间的相关性。我们的结果表明，在高青蒿素生产株（HAP）中，根和叶之间的染色体间相互作用的内染色体相互作用频率高于低青蒿素生产株（LAP）。我们发现，隔室转换与不同染色质之间的相互作用有关。有趣的是，腺毛分泌型腺体（GSTs）和青蒿素生物合成途径（ABP）相关基因在隔室转换区域富集，反映了青蒿素合成的调控。拓扑关联域边界与基因和表达水平的各种分布有关。与 ABP 和 GST 相关的基因在相邻环中高度表达，表明表观遗传调控在青蒿素合成和腺毛分泌型腺体产生过程中发挥重要作用。染色质结构在青蒿素合成过程中可能具有重要地位。
