Hager-Afos-TF-DNase
DNaseI profiles and ChIP-Seq profiles of GR and cJun in the presence and absence of A-fos
Dexamethasone treatment of cells at zero hour (untreated control) and 1 hour treatment times, in the absence and presence of acidic-fos (A-fos), an AP1 dominant negative. A-fos expression is under tetracycline control (Tet-off). ChIP-Seq for GR and cJun and DNaseI-Seq were performed in the various conditions. This is part of a larger study: Transcription Factor AP1 Potentiates Chromatin Accessibility and Glucocorticoid Receptor Binding.
Ligand-dependent transcription by the nuclear receptor glucocorticoid receptor (GR) is mediated by interactions with co-regulators. The role of these interactions in determining selective binding of GR to regulatory elements remains unclear.  Recent findings indicate a large fraction of genomic GR binding coincides with chromatin that is accessible prior to hormone treatment, suggesting that receptor binding is dictated by proteins that maintain chromatin in an open state.  Combining nucleolytic cleavage and chromatin immunoprecipitation with high-throughput sequencing, we identify the activator protein 1 (AP1) as a major partner for productive GR-chromatin interactions.  AP1 is critical for GR-regulated transcription and recruitment to co-occupied regulatory elements, illustrating an extensive AP1-GR interaction network. Importantly, the maintenance of baseline chromatin accessibility facilitates GR recruitment and is dependent on AP1 binding.  We propose a model where the basal occupancy of transcription factors act to prime chromatin and direct inducible transcription factors to select regions in the genome.