Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610065, Sichuan, China.
Clinical Medical Research Center, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
Nat Commun. 2024 Apr 3;15(1):2894. doi: 10.1038/s41467-024-47292-7.
Steroidal glycoalkaloids (SGAs) are major plant defense metabolites against pests, while they are considered poisonous in food. The genetic basis that guides negative selection of SGAs production during tomato domestication remains poorly understood. Here, we identify a distal enhancer, GAME Enhancer 1 (GE1), as the key regulator of SGAs metabolism in tomato. GE1 recruits MYC2-GAME9 transcriptional complex to regulate the expression of GAME cluster genes via the formation of chromatin loops located in the neighboring DNA region. A naturally occurring GE1 allelic variant is found to be more active in stimulating GAME expression. We show that the weaker GE1 allele has been the main driver for selecting reduced SGAs levels during tomato domestication. Unravelling the "TFs-Enhancer-Promoter" regulatory mechanism operating in SGAs metabolism opens unprecedented prospects for SGAs manipulation in Solanaceae via precision breeding strategies.
甾体糖苷生物碱（SGAs）是植物抵御害虫的主要防御代谢物，但它们在食物中被认为是有毒的。指导番茄驯化过程中对 SGA 产生进行负选择的遗传基础仍知之甚少。在这里，我们确定了一个远端增强子 GAME Enhancer 1（GE1），作为番茄中 SGA 代谢的关键调节剂。GE1 通过形成位于邻近 DNA 区域的染色质环，招募 MYC2-GAME9 转录复合物来调节 GAME 簇基因的表达。发现一种自然存在的 GE1 等位变体在刺激 GAME 表达方面更活跃。我们表明，较弱的 GE1 等位基因一直是番茄驯化过程中选择降低 SGA 水平的主要驱动因素。揭示在 SGA 代谢中起作用的“TFs-Enhancer-Promoter”调控机制，为通过精准育种策略在茄科植物中操纵 SGA 开辟了前所未有的前景。
