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) states vital for the differentiation of ES cells to multipotent stem cells. Recently a number of other chromatin states have been shown to exist in cell culture, including a repressive “Black” 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 the role chromatin states play in neural development, we used the Targeted DamID system to profile chromatin states within the developing fruit fly brain. We obtained genome-wide binding profiles of five key chromatin proteins in three separate cell types – neural stem cells (NSCs), immature neurons and mature neurons – and we determined chromatin states through a Hidden Markov Model approach.
We demonstrate that the majority of genes that are activated during neuronal differentiation are repressed by the Black chromatin state in NSCs. Furthermore, almost all key NSC genes are 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, our data suggest that forms of chromatin other than canonical PcG/TrxG transitions take over key roles during neural development.