Role of histone methylation in insect development: KMT5A regulates ecdysteroid biosynthesis during metamorphosis of Tribolium castaneum.

Methylation levels of core histones play important roles in the regulation of gene expression and impact animal development. However, the methyltransferases and demethylases that determine histone methylation levels remain largely unexplored in insects. Most of our current understanding of histone methylation comes from mammalian studies. In this study, we first identified potential histone methyltransferases and demethylases encoded in the genome of the red flour beetle Tribolium castaneum. The function of these histone methylation enzymes in the metamorphosis was investigated by knocking down genes coding for these enzymes using RNA interference (RNAi). Our results showed that a lysine methyltransferase, KMT5A, plays a critical role in T. castaneum metamorphosis by regulating the biosynthesis of ecdysteroids. Treating KMT5A-knockdown larvae with 20 hydroxyecdysone can partially rescue T. castaneum pupation. Western blot analysis showed that KMT5A catalyzes H4K20 mono-methylation. However, further studies suggest that KMT5A may regulate T. castaneum pupation through mechanisms independent of H4K20 methylation. These data uncovered the roles of histone methylation enzymes in T. castaneum metamorphosis and KMT5A as a critical regulator of ecdysteroid biosynthesis.