GSE162854
PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors
Radial glia (RG) in the neocortex sequentially generate distinct subtypes of projection neurons, accounting for the diversity and complex assembly of cortical neural circuits. Mechanisms that drive the rapid and precise temporal progression of RG are beginning to be elucidated. Here we reveal that the RG-specific transcriptional regulator PRDM16 promotes the transition of early to late phase of neurogenesis in the mouse neocortex. Loss of Prdm16 delays the timely progression of RG, leading to defective cortical laminar organization. Our genomic analyses demonstrate that PRDM16 regulates a subset of genes that are dynamically expressed between early and late neurogenesis. We show that PRDM16 suppresses target gene expression through limiting chromatin accessibility of permissive enhancers. We further confirm that critical target genes regulated by PRDM16 comprise neuronal specification genes, cell cycle regulators and molecules required for neuronal migration. These findings provide evidences to support that neural progenitors temporally shift gene expression program to achieve neural cell diversity. Overall design: To study the function of PRDM16 in gene regulation, ChIP-seq, RNA-seq and ATAC-seq datasets were generated to identify its genomic binding sites, gene expression change and chromatin accessibility change in the mutant versus wild-type control.