GAGA-associated factor fosters loop formation in the Drosophila genome.

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.

Genomic Analysis of Foxp3 Function in Regulatory T Cells.

Regulatory T (Treg) cells are critical for tolerance to self-antigens and for preventing autoimmunity. Foxp3 has been identified as a Treg cell lineage-defining transcription factor controlling Treg cell differentiation and function. In this article, we review the current mechanistic and systemic understanding of Foxp3 function enabled by experimental and computational advances in high-throughput genomics.