PT  - JOURNAL ARTICLE
AU  - Richa Arya
AU  - Seda Gyonjyan
AU  - Katherine Harding
AU  - Tatevik Sarkissian
AU  - Ying Li
AU  - Lei Zhou
AU  - Kristin White
TI  - A Cut/cohesin axis alters the chromatin landscape to facilitate neuroblast death
AID  - 10.1101/299164
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 299164
4099  - http://biorxiv.org/content/early/2018/04/10/299164.short
4100  - http://biorxiv.org/content/early/2018/04/10/299164.full
AB  - Precise control of cell death in the nervous system is essential for development. Spatial and temporal factors activate the death of Drosophila neural stem cells (neuroblasts) by controlling the transcription of multiple cell death genes through a shared enhancer, enh1. The activity of enh1 is controlled by abdominalA and Notch, but additional inputs are needed for proper specificity. Here we show that the Cut DNA binding protein is required for neuroblast death, acting downstream of enh1. In the nervous system, Cut promotes an open chromatin conformation in the cell death gene locus, allowing cell death gene expression in response to abdominalA. We demonstrate a temporal increase in global H3K27me3 levels in neuroblasts, which is enhanced by cut knockdown. Furthermore, cut regulates the expression of the cohesin subunit Stromalin in the nervous system. The cohesin components Stromalin and NippedB are required for neuroblast death, and knockdown of Stromalin increases repressive histone modifications in neuroblasts. Thus Cut and cohesin regulate apoptosis in the developing nervous system by altering the chromatin landscape.Summary statement Cut regulates the programmed death of neural stem cells by altering cohesin levels and promoting a more open chromatin conformation to allow cell death gene expression.