Glucocorticoid receptor wields chromatin interactions to tune transcription for cytoskeleton stabilization in podocytes

Elucidating transcription mediated by the glucocorticoid receptor (GR) is crucial for understanding the role of glucocorticoids (GCs) in the treatment of diseases. Podocyte is a useful model for studying GR regulation because GCs are the primary medication for podocytopathy. In this study, we integrated data from transcriptome, transcription factor binding, histone modification, and genome topology. Our data reveals that the GR binds and activates selective regulatory elements in podocyte. The 3D interactome captured by HiChIP facilitates the identification of remote targets of GR. We found that GR in podocyte is enriched at transcriptional interaction hubs and super-enhancers. We further demonstrate that the target gene of the top GR-associated super-enhancer is indispensable to the effective functioning of GC in podocyte. Our findings provided insights into the mechanisms underlying the protective effect of GCs on podocyte, and demonstrate the importance of considering transcriptional interactions in order to fine-map regulatory networks of GR. Wang et al. use several genome-wide approaches to investigate glucocorticoid receptor (GR) action in a podocyte cell line model. They conclude that direct GR bindings are enriched at super enhancers, highlighting a strategy potentially used by GR to regulate transcription through super-enhancers and long-range interactions.