A positive role of Sin3A in regulating Notch signaling during Drosophila wing development.

Notch is a transmembrane receptor that mediates intercellular signaling through a conserved signaling cascade in all animal species. Transcriptional and posttranscriptional regulation of Notch receptor are important for maintaining Notch signaling activity. Here, we show that depletion of Drosophila Sin3A leads to loss of the adult wing margin and downregulation of Notch target gene expression in the developing wing disc. Sin3A regulates the Notch pathway downstream of Delta and upstream of Notch activation. The role of Sin3A in the Notch pathway is partly mediated by its ability to modulate Notch receptor transcription. Furthermore, the transcriptional activation of Notch receptor is autoregulated by Notch itself. We also provide evidence that Sin3A is required for Notch activation mediated Notch transcription. Together, our data demonstrate that Sin3A activates Notch signaling by promoting Notch transcription and reveal a previously unknown autoregulatory mechanism for Notch signaling activation during Drosophila wing development.