Dynamics of RNA Polymerase II Pausing and Bivalent Histone H3 Methylation during Neuronal Differentiation in Brain Development

During cellular differentiation, genes important for differentiation are expected to be silent in stem/progenitor cells yet can be readily activated. RNA polymerase II (Pol II) pausing and bivalent chromatin marks are two paradigms suited for establishing such a poised state of gene expression; however, their specific contributions in development are not well understood. Here we characterized Pol II pausing and H3K4me3/H3K27me3 marks in neural progenitor cells (NPCs) and their daughter neurons purified from the developing mouse cortex. We show that genes paused in NPCs or neurons are characteristic of respective cellular functions important for each cell type, although pausing and pause release were not correlated with gene activation. Bivalent chromatin marks poised the marked genes in NPCs for activation in neurons. Interestingly, we observed a positive correlation between H3K27me3 and paused Pol II. This study thus reveals cell type-specific Pol II pausing and gene activation-associated bivalency during mammalian neuronal differentiation.