Miranda, Tina B2; Voss, Ty C2; Sung, Myong-Hee2; Baek, Songjoon2; John, Sam2; Hawkins, Mary2; Grøntved, Lars3; Schiltz, R Louis2; Hager, Gordon L2
1 Department of Biochemistry and Molecular Biology, Faculty of Science, SDU2 unknown3 Department of Biochemistry and Molecular Biology, Faculty of Science, SDU
interplay of the estrogen and glucocorticoid receptors at the genomic level
Cross-talk between estrogen receptors (ER) and glucocorticoid receptors (GR) has been shown to contribute to the development and progression of breast cancer. Importantly, the ER and GR status in breast cancer cells is a significant factor in determining the outcome of the disease. However, mechanistic details defining the cellular interactions between ER and GR are poorly understood. We investigated genome-wide binding profiles for ER and GR upon coactivation and characterized the status of the chromatin landscape. We describe a novel mechanism dictating the molecular interplay between ER and GR. Upon induction, GR modulates access of ER to specific sites in the genome by reorganization of the chromatin configuration for these elements. Binding to these newly accessible sites occurs either by direct recognition of ER response elements or indirectly through interactions with other factors. The unveiling of this mechanism is important for understanding cellular interactions between ER and GR and may represent a general mechanism for cross-talk between nuclear receptors in human disease.
Cancer Research, 2013, Vol 73, Issue 16, p. 5130-9
Animals; Binding Sites; Cell Line; Chromatin; DNA; Genome; Mice; Protein Binding; Receptors, Estrogen; Receptors, Glucocorticoid; Response Elements