Effects of loss and gain of KAT6B on gene expression in neural stem and progenitor cells [NSC_Kat6b_RNAseq]

High histone acetylation is associated with high transcriptional activity. The lysine acetyltransferase KAT6B is known to be required for histone acetylation and KAT6B is essential for normal brain development. In this study we examined the effects of loss and gain of KAT6B on gene expression in forebrain neural stem and progenitor cells (NSPCs). We isolated NSPCs from the dorsal telencephalon of embryonic day 12.5 embryos, which is the primordium of the cerebral cortex, from mouse embryos that lacked KAT6B or overexpressed KAT6B. We cultured the cells in vitro for 3 to 5 passages before isolating RNA for library production and RNA-sequencing. We found that genes required for neuronal differentiation and brain development were downregulated in Kat6b null cells and upregulated in Kat6b transgenic overexpressing cells. RNA levels in E12.5 dorsal telencephalon neural stem and progenitor cells were compared between (a) Kat6b–/– and wild-type cells and (b) Tg(Kat6b) cells, which overexpressed Kat6b mRNA approximately 4.5-fold, and wild-type cells. Kat6b–/– and wild-type cells were derived from mouse embryos on a C57BL/6 genetic background. Tg(Kat6b) and their and wild-type control cells were derived from mouse embryos on a mixed FVBxBALB/c background, because the Tg(Kat6b) mice were not viable on an inbred background.