A key question in developmental biology is how cellular differentiation is controlled during development. Particular interest has focused upon changes in chromatin state, with transitions between Trithorax-group (TrxG) and Polycomb-group (PcG) chromatin states shown to be vital for the differentiation of ES cells to multipotent stem cells in culture. Recent research has also suggested a number of other chromatin states exist in cell culture, including an active state lacking TrxG proteins and a repressive “Black” or “Null” chromatin state devoid of common chromatin marks. However, little is known as to the role of chromatin states during the development of complex organs such as the brain.

In order to understand how chromatin affects neural development, the recent Targeted DamID system was used to profile chromatin states in vivo within the developing fruit fly brain. Genome-wide binding profiles of five key chromatin proteins were obtained in three separate cell types: neural stem cells (NSCs), immature neurons and mature neurons. Chromatin states were determined through a Hidden Markov Model approach allowing the chromatin transitions occurring during the differentiation of NSCs into neurons to be investigated.

Surprisingly, the majority of genes that are activated during neuronal differentiation were repressed by the Black chromatin state and a novel TrxG-repressive state in neural stem cells (NSCs), indicating a clear role for these chromatin states in development. Furthermore, almost all key NSC genes were switched off via a transition to HP1-mediated repression. Interestingly, PcG-mediated repression does not play a significant role in regulating either of these transitions; instead, PcG chromatin specifically regulates lineage-specific transcription factors that control the spatial and temporal patterning of the brain. Combined, the data suggest that forms of chromatin other than canonical PcG/TrxG transitions take over key roles during neural development.