RFX5 Mediates High-order Structures to Regulate Cancer Progression-Associated Genes [RNA-Seq]

RFX5 is a DNA binding protein known to regulate MHC genes expressions with little studies on its role in maintaining 3D genome architecture. Recent studies have shown its potential in mediating long-range interactions in specific regions, though the underlying mechanism remains poorly understood. Here, using genes related to cancer progression as a paradigm, we studied the role of RFX5 and found that it specifically regulates these genes. It mediates interactions between gene promoters and their distal enhancers, which can be several hundreds of kilobases apart. We also found that RFX5 regulates higher-order structures of TADs and compartments, which become unstable upon loss of RFX5. Our findings elucidate the fundamental role of RFX5 in maintaining proper chromosome architecture and shed light on the relationship between chromatin loops and gene expression.