Histone deacetylases synergistically regulate juvenile hormone signaling in the yellow fever mosquito, Aedes aegypti

The yellow fever mosquito, Aedes aegypti, serves as the primary vector for transmitting deadly diseases such as dengue, yellow fever, chikungunya, and Zika fever. These viruses are spread by adult female mosquitoes during blood feeding on humans. Preventing the development of mosquitoes from the larval to adult stage could potentially stop the transmission of mosquito-borne diseases. In this context, two major hormones, Juvenile Hormones (JH) and ecdysteroids (with 20-hydroxyecdysone or 20E being the most active form), regulate this developmental transition. Recent studies have shown that histone acetylation plays a key role in the regulation of both JH and 20E signaling pathways. Histone acetylation is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Our previous research demonstrated that HDAC1, HDAC3, and HDAC11 regulate JH signaling in Tribolium castaneum. However, the role of these HDACs in JH signaling in Aedes aegypti remains unexplored. In this study, we found that the knockdown of HDAC1, HDAC4, and HDAC11 triggered JH signaling in Aag-2 cells derived from Aedes aegypti embryos. Moreover, simultaneous knockdown of these three HDACs synergistically enhanced the JH primary response gene Kr-h1, mimicking JH's action in inducing Kr-h1 expression. Our RNA sequencing results revealed that each HDAC regulates the transcription of distinct gene sets, though a few common genes involved in JH signaling were found across all three HDACs.