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Stage‐Specific H3K14 and H3K23 Succinylation Orchestrates Insect Metamorphosis and Oogenesis

Year: 2026

Type: article

Abstract: ABSTRACT Histone lysine succinylation is a pivotal epigenetic modification for diverse biological processes, yet how it regulates insect metamorphosis and reproduction remains poorly understood. Using Locusta migratoria as the primary model, we report here that protein succinylation is the most abundant acylation in the fat body, a highly metabolically active tissue analogous to vertebrate liver and adipose tissue. Succinylation of histone H3 on lysine 14 (suc‐H3 K14 ) is predominant in nymphs, whereas H3K23 succinylation (suc‐H3 K23 ) is highly abundant in adults. H3 K14A mutation causes embryonic lethality, and H3 K23A mutants exhibit remarkably reduced fecundity. P300 and GCN5 serve as succinyltransferases catalyzing suc‐H3 K14 and suc‐H3 K23 , respectively. While P300‐mediated suc‐H3 K14 is promoted via the GPCR‐PLC‐LTCC‐PKCα cascade, GCN5‐triggered suc‐H3 K23 is achieved through the GPCR‐PLC‐TTCC‐PKCε axis. Loss of P300 function and inhibition of suc‐H3 K14 lead to precocious metamorphosis. Knocking down GCN5 and suppression of suc‐H3 K23 result in blocked oogenesis. Cut&Tag‐seq reveals that suc‐H3 K14 and suc‐H3 K23 target the genes regulating metamorphosis and vitellogenesis, respectively. Furthermore, suc‐H3 K14 ‐repressed precocious metamorphosis and suc‐H3 K23 ‐stimulated reproduction are evolutionarily conserved across divergent insect orders. The study significantly advances our understanding of how stage‐specific H3K succinylations coordinate insect metamorphosis and oogenesis, filling a gap in the epigenetic regulation of key life‐history traits.

Source: Advanced Science

DOI: 10.1002/advs.75624