GAGA-associated factor fosters loop formation in the Drosophila genome

Xiao Li, Xiaona Tang, Xinyang Bing, Christopher Catalano, Taibo Li, Gabriel Dolsten, Carl Wu, Michael Levine

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


The impact of genome organization on the control of gene expression persists as a major challenge in regulatory biology. Most efforts have focused on the role of CTCF-enriched boundary elements and TADs, which enable long-range DNA-DNA associations via loop extrusion processes. However, there is increasing evidence for long-range chromatin loops between promoters and distal enhancers formed through specific DNA sequences, including tethering elements, which bind the GAGA-associated factor (GAF). Previous studies showed that GAF possesses amyloid properties in vitro, bridging separate DNA molecules. In this study, we investigated whether GAF functions as a looping factor in Drosophila development. We employed Micro-C assays to examine the impact of defined GAF mutants on genome topology. These studies suggest that the N-terminal POZ/BTB oligomerization domain is important for long-range associations of distant GAGA-rich tethering elements, particularly those responsible for promoter-promoter interactions that coordinate the activities of distant paralogous genes.

Original languageEnglish (US)
Pages (from-to)1519-1526.e4
JournalMolecular Cell
Issue number9
StatePublished - May 4 2023

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


  • GAGA-associated factor
  • POZ/BTB domain
  • Q-rich moiety
  • chromatin loop
  • long-range enhancer-promoter interactions
  • promoter-promoter associations connecting distant paralogous genes
  • tethering elements
  • toperons
  • topological operons


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