title: Transcription factor AP1 potentiates chromatin accessibility and glucocorticoid receptor binding.
abstract: Ligand-dependent transcription by the nuclear receptor glucocorticoid receptor (GR) is mediated by interactions with coregulators. The role of these interactions in determining selective binding of GR to regulatory elements remains unclear. Recent findings indicate that 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 DNaseI accessibility 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 in which the basal occupancy of transcription factors acts to prime chromatin and direct inducible transcription factors to select regions in the genome.
authors: Laboratory of Receptor Biology and Gene Expression, B602, Building 41, 41 Library Drive, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Simon C
authors: SC
authors: Biddie
authors: Sam
authors: S
authors: John
authors: Pete J
authors: PJ
authors: Sabo
authors: Robert E
authors: RE
authors: Thurman
authors: Thomas A
authors: TA
authors: Johnson
authors: R Louis
authors: RL
authors: Schiltz
authors: Tina B
authors: TB
authors: Miranda
authors: Myong-Hee
authors: MH
authors: Sung
authors: Saskia
authors: S
authors: Trump
authors: Stafford L
authors: SL
authors: Lightman
authors: Charles
authors: C
authors: Vinson
authors: John A
authors: JA
authors: Stamatoyannopoulos
authors: Gordon L
authors: GL
authors: Hager
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D016678:Genome; D008024:Ligands; D051379:Mice; D008957:Models, Genetic; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000378:metabolism*; D050436:Regulatory Elements, Transcriptional; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000502:physiology*
chemical_list: D002843:Chromatin; D008024:Ligands; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1