The spatial organization of genes in the interphase nucleus plays an important role in establishment and regulation of gene expression. However, little is known about genomic features of associating loci and how they relate to rapid transcriptional regulation by an inducible transcription factor. We combined genome-wide interaction profiling with expression, protein occupancy, and chromatin accessibility profiles, to investigate the properties of genomic loci that are in close proximity with glucocorticoid receptor (GR)-responsive loci. The transcriptional response to GR occurs without dramatic nuclear reorganization. Rather, the nucleus is pre-organized in a conformation allowing rapid transcriptional reprogramming by GR. Regions contacting GR-regulated genes were gene-rich and contained loci with different, and even opposite, transcriptional responses to GR. These hubs are not enriched for GR regulated loci, or any functional group of genes. These regions are, however, highly enriched for GR binding sites and DNaseI hypersensitive sites. These findings indicate that chromosomal segments containing GR regulatory elements and open chromatin are arranged in nuclear domains that are poised to respond to diverse signals in general, and permit efficient gene regulation.

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National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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