CREB-binding protein is required for epigenetic and hormonal regulation of Aedes aegypti metamorphosis

The yellow fever mosquito, Aedes aegypti, is a primary vector for many arboviruses and transmits deadly diseases such as dengue, yellow fever, chikungunya, zika fever, etc. These viruses transmitted to vertebrates including humans by adult female mosquitoes during a blood meal. Blocking mosquito transition from larva to an adult could prevent the transmission of mosquito-borne diseases. The concerted action of two major hormones, Juvenile hormones (JH) and ecdysteroids (20-hydroxyecdysone, 20E, is the most active form) regulates this transition. We found that a multi-functional transcription factor and epigenetic regulator, CREB-binding protein (CBP) plays a key role in Ae. aegypti larval-pupal metamorphosis by regulating JH and ecdysteroid signaling pathways. In this regard, we knockdown CBP in Ae. aegypti Aag-2 cells and performed RNA sequencing. Differential gene expression analysis of RNA-seq data identified approximately 2,100 transcripts that are differentially expressed (P-value <0.01 and >2-fold change) between the cells treated with double-stranded RNA targeting CBP (dsCBP) and dsRNA targeting maltose-binding protein (dsmalE-control). RNA sequencing analysis also revealed that CBP regulates many JH and 20E response genes differentially. We found that CBP is an essential player in JH and 20E action and regulate metamorphosis in Ae. aegypti.