Mapping the dynamics of the glucocorticoid receptor and its coregulator NCoA-2 in the nucleus.

STORTZ M; PRESMAN, D.M.; BRUNO, LUCIANA; ANNIBALE, PAOLO; HAGER, G; GRATTON, ENRICO; LEVI, V; PECCI A .

Congreso; LII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2019

SAIB

The distribution of the transcription machinery among different subnuclear domains raises the question on how this organization modulates the transcriptional response. We used imaging and fluorescence correlation spectroscopy (FCS) based approaches to quantitatively explore the dynamical intranuclear organization of the glucocorticoid receptor (GR) in living cells. This ligand-activated transcription factor diffuses within the nucleus and can engage in shorter and longer-lived interactions with chromatin targets or interact with DNA-dependent foci or promyelocytic leukemia (PML) bodies, which accumulate the coregulator NCoA-2. We also analyzed the recruitment and binding properties of GR and its coregulator to glucocorticoid response elements (GREs). The distribution of the receptor among these different nuclear compartments depends on the interaction with NCoA-2 and GR conformation, as assessed with synthetic ligands and receptor mutants with impaired transcriptional abilities. Our results suggest that the partition of the GR in different nuclear reservoirs may represent another step of transcription regulation, since the interaction with these compartments could ultimately influence the ability to bind to the specific transcriptional targets.