Chromatin architecture reorganisation during neuronal cell differentiation in Drosophila genome

ABSTRACT Compartmentalisation of the genome as topologically associating domains (TADs) may have 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 identified different classes of TADs by comparing this to genome organisation in embryonic cells (Kc167). We find new rearrangements during differentiation in neuronal cells reflected as enhanced long-range interactions, which is supported by pronounced enrichment of CTCF at cell type specific borders. Furthermore, we show the presence of strong divergent transcription corroborated with RNA Polymerase II occupancy and increased 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.