A study published in *Nature Genetics* (2011) reveals that chromatin accessibility pre-determines the binding patterns of the glucocorticoid receptor (GR), a key transcription factor. The research shows that up to 95% of GR binding sites are located in pre-existing regions of accessible chromatin. GR binding not only occurs in these regions but also enhances chromatin accessibility, indicating a feedback loop between GR and chromatin structure. The study used high-resolution mapping techniques, including digital DNaseI analysis and ChIP-seq, to examine GR occupancy and chromatin accessibility in mouse mammary adenocarcinoma (3134) and pituitary (AtT-20) cells. The results show that GR binding is highly dependent on pre-existing chromatin accessibility, with most GR sites located in regions that were accessible before hormone treatment. However, some GR binding sites occur in less accessible regions, suggesting that local sequence features also influence GR binding. The study also found that GR binding is cell-specific, with only a small fraction of GR sites shared between different cell types. This highlights the role of cell-specific chromatin landscapes in determining GR occupancy. The findings suggest that chromatin accessibility plays a dominant role in determining where transcription factors bind, and that this effect is modulated by local sequence features. The study also provides insights into the tissue-specific effects of steroid hormones, showing that cell-specific chromatin accessibility patterns explain the differences in hormone response between tissues. The results have implications for understanding how transcription factors interact with the genome and for developing more effective steroid-based therapies. The study underscores the importance of chromatin structure in regulating gene expression and highlights the potential for chromatin-based therapies in treating diseases.A study published in *Nature Genetics* (2011) reveals that chromatin accessibility pre-determines the binding patterns of the glucocorticoid receptor (GR), a key transcription factor. The research shows that up to 95% of GR binding sites are located in pre-existing regions of accessible chromatin. GR binding not only occurs in these regions but also enhances chromatin accessibility, indicating a feedback loop between GR and chromatin structure. The study used high-resolution mapping techniques, including digital DNaseI analysis and ChIP-seq, to examine GR occupancy and chromatin accessibility in mouse mammary adenocarcinoma (3134) and pituitary (AtT-20) cells. The results show that GR binding is highly dependent on pre-existing chromatin accessibility, with most GR sites located in regions that were accessible before hormone treatment. However, some GR binding sites occur in less accessible regions, suggesting that local sequence features also influence GR binding. The study also found that GR binding is cell-specific, with only a small fraction of GR sites shared between different cell types. This highlights the role of cell-specific chromatin landscapes in determining GR occupancy. The findings suggest that chromatin accessibility plays a dominant role in determining where transcription factors bind, and that this effect is modulated by local sequence features. The study also provides insights into the tissue-specific effects of steroid hormones, showing that cell-specific chromatin accessibility patterns explain the differences in hormone response between tissues. The results have implications for understanding how transcription factors interact with the genome and for developing more effective steroid-based therapies. The study underscores the importance of chromatin structure in regulating gene expression and highlights the potential for chromatin-based therapies in treating diseases.