Regulation of chlorogenic acid, flavonoid, and iridoid biosynthesis by histone H3K4 and H3K9 methylation in Lonicera jap

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ORIGINAL ARTICLE

Regulation of chlorogenic acid, flavonoid, and iridoid biosynthesis by histone H3K4 and H3K9 methylation in Lonicera japonica Tianrui Liu1 · Jian Yang1 · Shuang Liu1 · Yuyang Zhao1 · Junhui Zhou1 · Yan Jin1 · Luqi Huang1 · Yuan Yuan1 Received: 30 July 2020 / Accepted: 6 November 2020 © Springer Nature B.V. 2020

Abstract Lonicera japonica is used in Chinese herbal medicines with a wide spectrum of pharmacological properties associated with chlorogenic acid, flavonoid and iridoid. The biosynthesis of these compounds could be affected by genetic inheritance and epigenetic modification. However, the mechanisms that regulate the expression of genes involved in the biosynthesis of these compounds are rarely known. The results of qRT-PCR showed that the biosynthesis gene expression of these compounds was related to histone H3K4 and H3K9 methylation levels. These active compounds content of L. japonica were measured by UPLC-MS/MS. H3K4me3 showed a positive correlation with chlorogenic acid and loganic acid content, and H3K9me positively correlated with luteolin content. The correlation between histone methylation levels and the levels of luteolin and loganic acid in L. japonica from different producing areas validate the regulatory role of histone methylation in biosynthesis of bioactive compounds. Our study demonstrated a potential regulatory network of H3K9/H3K4 methylation to gene expression and content of secondary metabolites, and provided a basis for understanding the mechanism underlying the variation of major bioactive compounds in L. japonica. Keyword  Bioactive compounds · Different producing areas · Histone methylation · Lonicera japonica Abbreviations PAL Phenylalanine ammonia-lyase C4H Cinnamate 4-hydroxylase 4CL 4-Coumarate CoA ligase HQT Hydroxycinnamoyl-CoA quinate transferase CHI Chalcone isomerase Tianrui Liu, Jian Yang, and Shuang Liu contributed equally to this work. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1103​3-020-05990​-7) contains supplementary material, which is available to authorized users.

CHS Chalcone synthase IPP Isopentenyl pyrophosphate DMAPP Dimethylallyl diphosphate triammonium salt GPP Geranyl pyrophosphate GPPS GPP synthase GES Geraniol synthase G10H Geraniol-10-hydroxylase 10HGO 10-Hydroxygeraniol IS Iridoid synthase 5-azaC 5-Azacytidine ORFs Open reading frames HMT Histone methyltransferase

* Yuan Yuan [email protected]

Junhui Zhou jh‑[email protected]

Tianrui Liu [email protected]

Yan Jin [email protected]

Jian Yang [email protected]

Luqi Huang [email protected]

Shuang Liu [email protected]

1

Yuyang Zhao [email protected]



State Key Laboratory of Dao‑Di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of China

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HDT Histone demethylase H3K4me1/2/3 Monomethylation/dimethylation/trimethylation of histone H3 at lysine 4 H3K9me1/2/3 Monomethylation/dim