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

Molecular cell 2023 May 04

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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. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Xiao Li, Xiaona Tang, Xinyang Bing, Christopher Catalano, Taibo Li, Gabriel Dolsten, Carl Wu, Michael Levine. GAGA-associated factor fosters loop formation in the Drosophila genome. Molecular cell. 2023 May 04;83(9):1519-1526.e4