Deubiquitinase Nonstop regulates apoptosis by controlling the transcription of apoptosis related genes during Drosophila eye development

Nonstop (Not) is a deubiquitinase and works as an important component of deubiquitinase module (DUBm) of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) chromatin modifying complex. In Drosophila, the DUBm mediates de-monoubiquitination of H2Bub1, thereby promoting transcription elongation, however, the specific regulatory mechanism is still unclear. Our study showed that loss of nonstop (not) caused severe eye defect and induced apoptosis. We carried out RNA-seq and CUT&Tag analysis to indicate that Not regulated the de-monoubiquitination of H2BK120Ub and tri-methylation of H3K4 and H3K79 on TSS of pro-apoptotic gene rpr and apoptosis related genes drep2 and drep3 to mediate apoptotic events. Meanwhile Not also positively regulate the expression of an important eye developmental gene eyes shut. Together, our results confirm that Not directly regulates the transcription of apoptosis related genes by modifying H2B on TSS, which is crucial for the survival and development of ommatidium.