Chromatin state changes during neural development revealed by in vivo cell-type specific profiling

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. However, little is known as to the role of chromatin states during the development of complex organs such as the brain. 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”, “Basal” or “Null” chromatin state devoid of common chromatin marks. The role that these new chromatin states play during development is unknown. Here we show that large scale chromatin remodeling occurs during in vivo Drosophila melanogaster neural development. We demonstrate that the majority of genes that are activated during neuronal differentiation are repressed by the Null chromatin state and a novel TrxG-repressive state in neural stem cells (NSCs). Furthermore, almost all key NSC genes are switched off via a direct transition to HP1-mediated repression. In contrast to previous studies of ES cell to neural progenitor cell development, 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. Overall design: Targeted DamID. Six samples per condition: Brm-Dam, Pc-Dam, HP1a-Dam, H1-Dam, RPII215-Dam (polII-Dam) and Dam alone. Two biological replicates for wor-GAL4, two or three biological replicates for GMR71C09-GAL4, three or four biological replicates for elav-GAL4.