Epigenetic Regulation of Juvenile Hormone

Post-translational modifications especially acetylation and deacetylation of histones and other proteins modulate hormone action. In Tribolium castaneum TcA cells, trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC) mimics juvenile hormones (JH) in induction of JH-response genes including Kr-h1 suggesting that HDACs may be involved in JH action. To test this hypothesis, we identified HDACs in T. castaneum and studied their function in growth and development. Knockdown of 12 HDAC genes identified in T. castaneum genome showed variable phenotypes; the most severe phenotype was detected in insects injected with double-stranded RNA targeting HDAC1 (dsHDAC1). The dsHDAC1 injected larvae, pupae and adults showed arrested growth and development and died. Application of JH analog, hydroprene or JH III to T. castaneum larvae or TcA cells respectively suppressed HDAC1 expression. Sequencing of RNA from control and dsHDAC1 injected larvae followed by differential gene expression analysis identified 1720 genes (≥2-fold difference and a p-value ≤ 0.05). The acetylation levels of core histones increased in dsHDAC1 treated TcA cells and larvae.