Figure 1. Recruitment of GR to response elements and activation of gene expression.

A. GR recruitment at the MMTV promoter. A schematic representation of GR-mediated transcriptional activation. Upon activation, GR is recruited to the MMTV LTR, which contains six nucleosomes labeled A–F. GR binds to nucleosome B and recruits the Swi/Snf chromatin remodeling complex, and removes the nucleosome at this position. Nucleosome removal creates a permissive chromatin environment for the binding of other regulatory factors and the RNA Polymerase II (PolII) complex leading to transcriptional activation of the downstream Ras reporter gene.

B. Spatial arrangement and long-range interactions between GR response elements and promoters. Depiction of chromosome territories spatially arranged in the nucleus. These arrangements contain transcription hubs, which harbor steroid receptor binding sites, allowing for long range inter- and intra-chromosomal interactions. Within these hubs are bound transcription factors (yellow boxes), which help maintain spatial orientation of the chromosomes as well as accessibility at GR binding sites. This pre-established configuration allows for GR to rapidly control the expression of genes found up to 50–100 kb away from the GR response element.

C. Mechanisms that recruit GR to specific sites in the genome. Similar to the mechanism described in Figure 1A, depicted are GR binding events at de novo sites in the genome and recruitment of chromatin remodelers. Chromatin modifiers remodel chromatin at these sites allowing for other transcription factors to bind in a mechanism known as an assisted loading. In contrast, GR can bind to pre-accessible sites and, at many of these sites, the accessibility has been shown to be dependent upon other regulatory factors being activated or expressed in a cell. GR can also co-bind to sites with other factors through tethering, in addition to cooperative binding at specific sites.