1. Mapping the Dynamics of the Glucocorticoid Receptor within the Nuclear Landscape

MARTIN STORTZ, DIEGO M. PRESMAN, LUCIANA BRUNO, PAOLO ANNIBALE, MARIA V. DANSEY, GERARDO BURTON, ENRICO GRATTON, ADALI PECCI AND VALERIA LEV

Scientific Reports

Nature Publishing Group

Año: 2017

2045-2322

The distribution of the transcription machineryamong different sub-nuclear domains raises the question on how the architectureof the nucleus modulates the transcriptional response. Here, we usedfluorescence fluctuation analyses to quantitatively explore the organization ofthe glucocorticoid receptor (GR) in the interphase nucleus of living cells. Wefound that this ligand-activated transcription factor diffuses within thenucleus and dynamically interacts with promyelocytic leukemia (PML) bodies,DNA-dependent foci and chromatin targets. The distribution of the receptoramong the nuclear compartments depends on the coregulator NCoA-2 and theconformation of the receptor as assessed with synthetic ligands and GR mutants withimpaired transcriptional abilities. Our results suggest that the partition ofthe receptor in different nuclear reservoirs ultimately regulates theconcentration of receptor available for the interaction with specific targets,and thus has an impact on transcription regulation