Chromatin architecture reorganization during neuronal cell differentiation in Drosophila genome

The organization of the genome into topologically associating domains (TADs) was shown to have a regulatory role in development and cellular function, but the mechanism involved in TAD establishment is still unclear. Here, we present the first high-resolution contact map of Drosophila neuronal cells (BG3) and identify different classes of TADs by comparing this to genome organization in embryonic cells (Kc167). We find that only some TADs are conserved in both cell lines, whereas the rest are cell-type–specific. This is supported by a change in the enrichment of architectural proteins at TAD borders, with BEAF-32 present in embryonic cells and CTCF in neuronal cells. Furthermore, we observe strong divergent transcription, together with RNA Polymerase II occupancy and an increase in DNA accessibility at the TAD borders. 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.