Chromatin architecture reorganisation during neuronal cell differentiation in Drosophila genome

Compartmentalisation of the genome as topologically associating domains (TADs) may have a regulatory role in development and cellular functioning, but the mechanism involved in TAD establishment is still unclear. Here, we present the first high-resolution contact map of Drosophila melanogaster neuronal cells (BG3) and identify different classes of TADs by comparing this to genome organisation in embryonic cells (Kc167). We find new interactions during differentiation in neuronal cells, which are reflected as enhanced long-range interactions. This is supported by pronounced enrichment of CTCF at TAD borders. Furthermore, we observed strong divergent transcription, together with RNA Polymerase II occupancy, and an increase in DNA accessibility at the TAD borders. Interestingly, TAD borders that are specific to neuronal cells are enriched in enhancers controlled by neuronal specific transcription factors. Our results suggest that TADs are dynamic across developmental stages and reflect the interplay between insulators, transcriptional states and enhancer activities. Comparison of Hi-C data in Drosophila melanogaster cell lines: BG3 (derived from larval central nervous system) and Kc167 (embryo derived)