DYNAMICAL ORGANIZATION OF THE GLUCOCORTICOID RECEPTOR IN DISCRETE NUCLEAR FOCI

PRESMAN, DIEGO M; PECCI, ADALI; GRATTON, ENRICO; STORTZ, MARTIN; LEVI, VALERIA

Bariloche

Simposio; The Fourth South American Symposium in Signal Transduction and Molecular Medicine; 2018

SISTAM

The cell nucleus is a compartmentalized organelle, with open membrane-less reservoirs in contact with the nucleoplasm. Transcription, as other nuclear functions, is a compartmentalized process. Many transcription factors (TF) exhibit a non-homogeneous distribution in the nucleus and form multiple discrete foci with a higher TF concentration. This is the case of the glucocorticoid receptor (GR), a ligand-activated TF. Despite that GR foci were described two decades ago their function still remains unknown. Recruitment to foci is ligand-dependent and is completely reversible. The exchange of GR molecules between these foci and the nucleoplasm is highly dynamic. The activated receptor can also interact with other partners within these foci, such as the nuclear receptor coactivator NCoA-2. GR foci distribution depends on DNA integrity but is not perturbed by a global chromatin decondensation agent. Time-lapse assays of consecutive ligand stimulation, hormone washout and ligand re-stimulation reveal a recruitment of activated GR to particular locations along the nucleus, thus suggesting the existence of pre-determined foci nucleating sites. The formation of TF foci stresses the relevance of spatial distribution of biomolecules in signaling and biochemical reactions within the cell, since these reservoirs may affect TF availability and functionality at enhancer sites.