A Cut/cohesin axis alters the chromatin landscape to facilitate neuroblast death

Area of Science:

• Developmental Biology
• Neuroscience
• Cell Biology

Background:

• Precise control of programmed cell death (apoptosis) is vital for nervous system development.
• In *Drosophila* (fruit fly), neural stem cells (neuroblasts) undergo apoptosis, regulated by specific genes controlled by a shared enhancer.
• Transcription factors *abdominal A* and *Notch* influence this enhancer, but additional factors are needed for precise regulation.

Purpose of the Study:

• To investigate the role of the Cut DNA-binding protein in *Drosophila* neuroblast apoptosis.
• To identify downstream targets and regulatory mechanisms of Cut in neuroblast death.
• To explore the involvement of cohesin in Cut-mediated apoptosis and chromatin regulation.

Main Methods:

• Gene expression analysis of cell death genes (*reaper*, *grim*) in response to *cut* manipulation.
• Chromatin immunoprecipitation followed by sequencing (ChIP-seq) to assess H3K27me3 modifications.
• RNA interference (RNAi) to knock down *cut* and *Stromalin* expression.
• Analysis of neuroblast temporal progression and apoptosis rates.

Main Results:

• Cut is essential for neuroblast death, regulating *reaper* and *grim* expression downstream of *abdominal A*.
• Loss of *cut* accelerates neuroblast transition to a high H3K27me3 state, with increased H3K27me3 at cell death gene loci.
• Cut regulates the cohesin subunit Stromalin; both Cut and cohesin (Stromalin, Nipped-B) are required for neuroblast death.
• Stromalin knockdown also increases H3K27me3 levels in neuroblasts.

Conclusions:

• Cut and cohesin are key regulators of apoptosis in the developing *Drosophila* nervous system.
• They function by modulating the chromatin landscape, specifically altering H3K27me3 levels at target gene loci.
• This mechanism ensures proper temporal control of neuroblast development and survival.