Epigenetic changes of chromatin are increasingly recognized as key modifications that dictate the differentiation state of cells during development. Within the central nervous system, extracellular cues induce chromatin remodelling events that are essential for neuronal progenitor proliferation, cell differentiation and, later, plasticity. In this review, we discuss recent studies that show how extracellular and intranuclear signals influence chromatin remodelling and neuron-specific gene expression. The gaseous molecule Nitric Oxide (NO) has recently emerged as a new key player that mediates the epigenetic changes associated with cell cycle arrest and differentiation in neurons. Histone deacetylases (HDACs) are the first identified intranuclear targets of NO, but, due to its highly diffusible nature, it is likely that many other nuclear factors are directly regulated by NO.