Microsatellite expansion redirects chromatin modifiers to confer insect resistance to Bt bioinsecticides

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.