SWI/SNF ATPase Brahma and Notch signaling collaborate with CBP/p300 to regulate neural stem cell apoptosis in Drosophila larval central nervous system.

SWI-SNF ATPase Brahma and Notch signalling are known to interact during development, but how this interaction is executed at the molecular level is not fully understood. We have investigated the molecular mechanism of Brm-Notch interaction in the context of Hox-dependent neural stem cell (NSC) apoptosis in the developing Central Nervous System (CNS) of Drosophila. Our results suggest a multi-tier regulation of NSC apoptosis by Brahma, first by regulating the expression of Drosophila CBP/p300 (Nejire) and the molecular triggers of cell death (Hox, bHLH factor Grainyhead, and Notch signalling pathway). The second mode of regulation is by direct binding of Brahma to the apoptotic enhancer and its collaboration with Notch signalling pathway to regulate the RHG family of apoptotic genes, grim and reaper. Our data support a model where, upon activation of Notch signaling, Brahma and CSL-Su(H)/Mastermind complex recruit CBP/p300 onto the apoptotic enhancer. This increases the H3K27ac marks on the nucleosomes to open up the chromatin and facilitate apoptotic gene transcription in Abd-B and Grh dependent manner.