Transcription factors form a ternary complex with NIPBL/MAU2 to localize cohesin at enhancers

While the cohesin complex is a key player in genome architecture, how it localizes to specific chromatin sites is not well understood. Recently, we and others have proposed that direct interactions with transcription factors (TFs) lead to the localization of the cohesin-loader complex (NIPBL/MAU2) within enhancers. Here, we identify two clusters of protein-protein interaction (PPI) motifs within the NIPBL sequence that regulate NIPBL dynamics, interactome, and NIPBL-dependent transcriptional programs. These PPIMs directly interact with chromatin-associated proteins, including TFs and one of them is necessary for the maintenance of the NIPBL-MAU2 heterodimer. Finally, using the glucocorticoid receptor (GR) as a model, we investigate its interaction surfaces with NIPBL and MAU2 using AlphaFold2 and surface plasmon resonance to uncover a TF-NIPBL-MAU2 ternary complex and present its importance in GR-dependent gene regulation.