Cheng Yufei, Ning Kang, Chen Yongzhong, Hou Cong, Yu Haibin, Yu Huatao, Chen Shilin, Guo Xiaotong, Dong Linlin
Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
College of Agronomy, Ludong University, Yantai, 264000, China.
Chin Med. 2023 Feb 13;18(1):16. doi: 10.1186/s13020-023-00720-0.
Histone acetyltransferases (HATs) play an important role in plant growth and development, stress response, and regulation of secondary metabolite biosynthesis. Hemp (Cannabis sativa L.) is famous for its high industrial, nutritional, and medicinal value. It contains non-psychoactive cannabinoid cannabidiol (CBD) and cannabinol (CBG), which play important roles as anti-inflammatory and anti-anxiety. At present, the involvement of HATs in the regulation of cannabinoid CBD and CBG synthesis has not been clarified.
The members of HAT genes family in hemp were systematically analyzed by bioinformatics analysis. In addition, the expression level of HATs and the level of histone acetylation modification were analyzed based on transcriptome data and protein modification data. Real-time quantitative PCR was used to verify the changes in gene expression levels after inhibitor treatment. The changes of CBD and CBG contents after inhibitor treatment were verified by HPLC-MS analysis.
Here, 11 HAT genes were identified in the hemp genome. Phylogenetic analysis showed that hemp HAT family genes can be divided into six groups. Cannabinoid synthesis genes exhibited spatiotemporal specificity, and histones were acetylated in different inflorescence developmental stages. The expression of cannabinoid synthesis genes was inhibited and the content of CBD and CBG declined by 10% to 55% in the samples treated by HAT inhibitor (PU139). Results indicated that CsHAT genes may regulate cannabinoid synthesis through altering histone acetylation.
Our study provides genetic information of HATs responsible for cannabinoid synthesis, and offers a new approach for increasing the content of cannabinoid in hemp.
组蛋白乙酰转移酶（HATs）在植物生长发育、应激反应以及次生代谢物生物合成调控中发挥重要作用。大麻（Cannabis sativa L.）以其高工业、营养和药用价值而闻名。它含有非精神活性大麻素大麻二酚（CBD）和大麻酚（CBG），具有抗炎和抗焦虑的重要作用。目前，HATs在大麻素CBD和CBG合成调控中的作用尚未明确。
通过生物信息学分析对大麻中HAT基因家族成员进行系统分析。此外，基于转录组数据和蛋白质修饰数据分析HATs的表达水平以及组蛋白乙酰化修饰水平。采用实时定量PCR验证抑制剂处理后基因表达水平的变化。通过高效液相色谱 - 质谱分析验证抑制剂处理后CBD和CBG含量的变化。
在此研究中，在大麻基因组中鉴定出11个HAT基因。系统发育分析表明，大麻HAT家族基因可分为六组。大麻素合成基因表现出时空特异性，并且在不同的花序发育阶段组蛋白发生乙酰化。在HAT抑制剂（PU139）处理的样品中，大麻素合成基因的表达受到抑制，CBD和CBG含量下降了10%至55%。结果表明，CsHAT基因可能通过改变组蛋白乙酰化来调控大麻素合成。
我们的研究提供了负责大麻素合成的HATs的遗传信息，并为提高大麻中大麻素含量提供了新方法。
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