Chromosome-level organization of the regulatory genome in the Drosophila nervous system [scRNA-seq]

We present evidence for a new level of genome folding, whereby distant domains megabases apart fuse to form meta-domains. Within meta-domains, certain gene promoters pair with structural intergenic elements in the distant TAD. These long-range associations occur in a large fraction of Drosophila neurons, but support transcription in only a subset of cells in the nervous system. Most of the associated genes encode neuronal determinants, including those engaged in axonal guidance and adhesion. We used single cell RNA sequencing (scRNA-seq) to analyze gene misexpression genotypes after deleting intergenic meta-loop anchors. Drosophila melanogaster third instar larval central nervous systems (CNS) of wildtype animals or animals homozygous for a precise deletion of an intergenic meta-loop anchor were dissected and analyzed by scRNA-seq.