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

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

PROVIDER: PRJNA886715 | ENA |

REPOSITORIES: ENA

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Chromosome-level organization of the regulatory genome in the Drosophila nervous system

Project description:Chromosome-level organization of the regulatory genome in the Drosophila nervous system

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

Project description: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.

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Project description:Past studies have identified topologically associating domains (TADs) as basic units of genome organization. Here, we present evidence for a new level of genome folding, whereby distant TAD pairs megabases apart interact to form meta-domains. Within meta-domains, gene promoters and structural intergenic elements present in distant TADs are specifically paired. The associated genes encode neuronal determinants, including those engaged in axonal guidance and adhesion. These long-range associations occur in a large fraction of neurons but support transcription in only a subset of neurons. Meta-domains are formed by diverse transcription factors that are able to pair over long and flexible distances. We present evidence that two such factors, GAF and CTCF, play direct roles in this process. The relative simplicity of higher-order meta-domain interactions in Drosophila, compared with those previously described in mammals, allowed the demonstration that genomes can fold into highly specialized cell type-specific scaffolds that enable megabase-scale regulatory associations.

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Chromosome-level organization of the regulatory genome in the Drosophila nervous system [Hi-C]

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