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Article|31 May 2023|OPEN
Characteristics of Salvia miltiorrhiza methylome and the regulatory mechanism of DNA methylation in tanshinone biosynthesis
Jiang Li1,2 ,† , Caili Li1,2 ,† and Yuxing Deng1,2 , Hairong Wei3 , Shanfa Lu,1,2 ,
1Key Lab of Chinese Medicine Resources Conservation, State Administration of Traditional Chinese Medicine of the People’ s Republic of China, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
2Engineering Research Center of Chinese Medicine Resource, Ministry of Education, Beijing 100193, China
3College of Forest Resources and Environmental Science, Michigan Technological University, Houghton, MI 49931, USA
*Corresponding author. E-mail:
Both authors contributed equally to the study.

Horticulture Research 10,
Article number: uhad114 (2023)
Views: 117

Received: 17 Nov 2022
Accepted: 21 May 2023
Published online: 31 May 2023


Salvia miltiorrhiza is a model medicinal plant with significant economic and medicinal value. Its roots produce a group of diterpenoid lipophilic bioactive components, termed tanshinones. Biosynthesis and regulation of tanshinones has attracted widespread interest. However, the methylome of S. miltiorrhiza has not been analysed and the regulatory mechanism of DNA methylation in tanshinone production is largely unknown. Here we report single-base resolution DNA methylomes from roots and leaves. Comparative analysis revealed differential methylation patterns for CG, CHG, and CHH contexts and the association between DNA methylation and the expression of genes and small RNAs. Lowly methylated genes always had higher expression levels and 24-nucleotide sRNAs could be key players in the RdDM pathway in S. miltiorrhiza. DNA methylation variation analysis showed that CHH methylation contributed mostly to the difference. Go enrichment analysis showed that diterpenoid biosynthetic process was significantly enriched for genes with downstream overlapping with hypoCHHDMR in July_root when comparing with those in March_root. Tanshinone biosynthesis-related enzyme genes, such as DXS2CMKIDI1HMGR2DXRMDSCYP76AH1, 2OGD25, and CYP71D373, were less CHH methylated in gene promoters or downstream regions in roots collected in July than those collected in March. Consistently, gene expression was up-regulated in S. miltiorrhiza roots collected in July compared with March and the treatment of DNA methylation inhibitor 5-azacytidine significantly promoted tanshinone production. It suggests that DNA methylation plays a significant regulatory role in tanshinone biosynthesis in S. miltiorrhiza through changing the levels of CHH methylation in promoters or downstreams of key enzyme genes.