A model of glucocorticoid receptor interaction with coregulators predicts transcriptional regulation of target genes

CHATZOPOULOU, ANTONIA; MEIJER, ONNO C.; ZAPPIA, CARLOS DANIEL; FITZSIMONS, CARLOS P.; MONCZOR, FEDERICO; HOUTMAN, RENÉ

Frontiers in Pharmacology

Frontiers Media S.A.

Lugar: Lausanne; Año: 2019 vol. 10

Regulatory factors that control gene transcription in multicellular organisms are assembled in multicomponent complexes by combinatorial interactions. In this context, nuclear receptors provide well-characterized and physiologically relevant systems to study ligand-induced transcription resulting from the integration of cellular and genomic information in a cell- and gene-specific manner. Here, we developed a mathematical model describing the interactions between the glucocorticoid receptor (GR) and other components of a multifactorial regulatory complex controlling the transcription of GR-target genes, such as coregulator peptides. We support the validity of the model in relation to gene-specific GR transactivation with gene transcription data from A549 cells and in vitro real time quantification of coregulator-GR interactions. The model accurately describes and helps to interpret ligand-specific and gene-specific transcriptional regulation by the GR. The comprehensive character of the model allows future insight into the function and relative contribution of the molecular species proposed in ligand- and gene-specific transcriptional regulation.