微卫星扩增重定向染色质修饰因子使小菜蛾对 Bt 生物杀虫剂产生抗性
Microsatellite expansion redirects chromatin modifiers to confer insect resistance to Bt bioinsecticides
研究发现，小菜蛾 ABCC2 基因启动子区的四核苷酸（ATGT）微卫星扩增可通过表观遗传机制沉默该基因表达，从而赋予其对 Bt Cry1Ac 毒素的抗性。机制上，抗性品系中长重复序列（≥27 个单元）优先招募组蛋白甲基转移酶 E(z)，促进 H3K27me2/3 沉积、染色质压缩和转录沉默；而敏感品系中的短重复序列则通过 Tip60 介导的 H4K5 乙酰化维持开放染色质。该重复扩增本身足以抑制 ABCC2 并导致 Bt 抗性，且在放松选择压力下，重复长度、染色质状态及相关表型可部分回复。研究将微卫星驱动的染色质重塑定义为昆虫快速异源物质抗性进化中一种普遍且可塑的调控策略。
来源：Nucleic Acids Research · doi.org
Microsatellites are highly mutable genomic elements, yet their role in adaptive gene regulation in insects remains poorly understood. Here, we show that a tetranucleotide (ATGT) microsatellite expansion in the promoter of ABCC2, a key Bacillus thuringiensis (Bt) toxin receptor gene, epigenetically silences its expression and confers resistance to Bt Cry1Ac toxin in Plutella xylostella (L.). Mechanistically, long repeats (≥27 units) in Cry1Ac-resistant strains preferentially recruit the histone methyltransferase E(z), promoting H3K27me2/3 deposition, chromatin compaction, and transcriptional silencing, whereas short repeats in susceptible strains maintain open chromatin through Tip60-mediated H4K5 acetylation. This repeat expansion alone is sufficient to repress ABCC2, thereby conferring Bt resistance, while repeat length, chromatin state, and associated phenotypes partially revert under relaxed selection. These findings define a previously uncharacterized cis-acting element dynamically orchestrating insecticide resistance-associated gene expression and identify microsatellite-driven chromatin remodeling as a general and plastic regulatory strategy underlying rapid xenobiotic-resistance evolution in insects.