Chromatin Remodeler Dmp18 regulates apoptosis by controlling H2Av incorporation into pro-apoptotic genes in Drosophila imaginal disc development

Programmed Cell Death (PCD) or apoptosis is a highly conserved biological process and plays essential roles both in development and stress context. In Drosophila, up-regulation of pro-apoptotic genes, including reaper (rpr), head involution defective (hid), grim and sickle (skl), is sufficient to induce cell death. Here, we demonstrate that the chromatin remodeler Dmp18, the homolog of mammalian Znhit1, plays a crucial role in regulating apoptosis by controlling transcription of pro-apoptotic genes during eye and wing development. We found that deletion of Dmp18 disrupts eye and wing development. Loss of Dmp18 up-regulates the transcription of pro-apoptotic genes and induces apoptosis. Inhibition of apoptosis significantly suppresses the eye defects caused by Dmp18 deletion. Furthermore, our study shows that loss of Dmp18 disrupts the histone variant H2Av incorporation into TSS regions of pro-apoptotic genes and increases the histone modification of H3K4me3 on TSS regions for subsequent transcriptional activation reguation. Together, our study indicates that Dmp18 negatively regulates apoptosis by controlling H2Av incorporation into TSS regions of pro-apoptotic genes. Our study establishes the dominant role of Dmp18/H2Av in Drosophila eye and wing development and provides a new insight into chromatin remodeling factor in regulating apoptosis at epigenetic level.