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

Giriram Mohana, Julien Dorier, Xiao Li, Marion Mouginot, Rebecca C. Smith, Héléna Malek, Marion Leleu, Daniel Rodriguez, Jenisha Khadka, Patrycja Rosa, Pascal Cousin, Christian Iseli, Simon Restrepo, Nicolas Guex, Brian D. McCabe, Aleksander Jankowski, Michael S. Levine, Maria Cristina Gambetta

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Previous studies have identified topologically associating domains (TADs) as basic units of genome organization. We present evidence of a previously unreported level of genome folding, where 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.

Original languageEnglish (US)
Pages (from-to)3826-3844.e26
Issue number18
StatePublished - Aug 31 2023

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology


  • Drosophila
  • TAD
  • chromosomal loop
  • gene regulation
  • genome architecture
  • genome organization
  • nervous system
  • neuron
  • transcription


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