Hallmarks of glucocorticoid receptor condensates involvement in transcription regulation

Abstract

Several proteins necessary for mRNA production concentrate in intranuclear condensates, which are proposedto affect transcriptional output. The glucocorticoid receptor (GR) is a ligand-activated transcriptionfactor that regulates the expression of hundreds of genes relevant to many physiological and pathologicalprocesses. As with all members of the steroid receptor family, GR forms condensates of unknown function.Here, we examine whether GR condensates are involved in transcription regulation using Airyscan super-resolutionmicroscopy and nano-antibodies targeting initiation and elongating states of RNA polymerase II(Pol2). We observed subpopulations of GR condensates colocalizing with initiating and, surprisingly, elongatingPol2 foci. The analysis of GR mutants with different transcriptional outputs suggests a correlation betweencondensate formation capability and transcription initiation. Moreover, the number of GR moleculeswithin initiation and elongation condensates appears to be linked to transcriptional activity. Taken together,our data suggests an involvement of GR condensates in transcription initiation and elongation.