Krüppel homolog 1 represses insect ecdysone biosynthesis by directly inhibiting the transcription of steroidogenic enzymes

Abstract

In insects, juvenile hormone (JH) and the steroid hormone ecdysone have opposing effects on regulation of the larval-pupal transition. Although increasing evidence suggests that JH represses ecdysone biosynthesis during larval development, the mechanism underlying this repression is not well understood. Here, we demonstrate that the expression of the Krüppel homolog 1 (Kr-h1), a gene encoding a transcription factor that mediates JH signaling, in ecdysone-producing organ prothoracic gland (PG) represses ecdysone biosynthesis by directly inhibiting the transcription of steroidogenic enzymes in both and Application of a JH mimic on ex vivo cultured PGs from and larvae induces expression and inhibits the transcription of steroidogenic enzymes. In addition, PG-specific knockdown of promotes-while overexpression hampers-ecdysone production and pupariation. We further find that Kr-h1 inhibits the transcription of steroidogenic enzymes by directly binding to their promoters to induce promoter DNA methylation. Finally, we show that Kr-h1 does not affect DNA replication in PG cells and that the reduction of PG size mediated by overexpression can be rescued by feeding ecdysone. Taken together, our data indicate direct and conserved Kr-h1 repression of insect ecdysone biosynthesis in response to JH stimulation, providing insights into mechanisms underlying the antagonistic roles of JH and ecdysone.

Myoglianin triggers the premetamorphosis stage in hemimetabolan insects

“…Our data indicate that high expression of myo correlates with high expression of ecdysone biosynthesis genes like nvd, phm, and dib. This may be due to the inhibition of Myo on jhamt expression, and thus on JH production and concomitant Kr-h1 expression, because Kr-h1 has been shown to repress the expression of ecdysteroidogenic enzyme genes (37,38). In any case, the high expression of Myo in N5 surely contributes to the production of the large, metamorphic ecdysone pulse in N6.…”

“…Recent reports indicate that JH can inhibit ecdysone production in holometabolan insects, such as the fly D. melanogaster and the silkmoth Bombyx mori. The effect is mediated by Kr-h1, which represses the expression of ecdysteroidogenic genes (37,38). Therefore, it is plausible that the reduced expression of nvd, phm, and dib in dsMyo-treated cockroaches could be due to an increase in Kr-h1 expression resulting from Myo depletion ( Fig.…”

“…This supports the hypothesis that FTZ-F1 helps enhance phm and dib transcription in the PG of B. germanica. Finally, decreased expression of ecdysteroidogenic genes in Myodepleted insects might be mediated by the increased expression of jhamt and Kr-h1 because JH and Kr-h1 inhibit the expression of these genes (37,38). We explored this possibility through experiments examining Myo in N6.…”

Juvenile hormone signaling – a mini review

“…Hence, JH suppresses ecdysone biosynthesis and inhibits metamorphosis, whereas 20E suppresses JH biosynthesis and promotes metamorphosis. Antagonistic actions of JH and 20E at the hormone‐biosynthesis levels determine developmental transitions in D. melanogaster (Liu et al ., ; Zhang et al ., ).…”

RNA interference‐mediated knockdown of the transcription factor Krüppel homologue 1 suppresses vitellogenesis in Chilo suppressalis

“…Furthermore, Kr‐h1 directly binds to the Kr‐h1 binding site (KBS) located in the E93 and BR‐C promoter regions to repress their transcription, thereby preventing metamorphosis (Kayukawa et al, ; Kayukawa et al, ). Also, Kr‐h1 down‐regulates ecdysone biosynthesis by binding directly to potential KBS in the promoters of steroidogenic enzyme genes in Drosophila and Bombyx , thereby restraining transcription of steroidogenic enzymes (Zhang et al, ). Expression levels of Kr‐h1 differ amongst different insect species and developmental stages.…”