title: Transcription factor interactions in genomic nuclear receptor function.
abstract: Transcription factors (TF) regulate gene expression acting as DNA sequence-specific binding factors, orchestrating cofactor recruitment and assembly of the transcriptional machinery. Nuclear receptors, a ligand-inducible TF class, regulate a large proportion of the genome, yet achieve highly cell-specific and context-dependent transcription, despite their widespread expression. High-throughput genome-wide profiling of TF binding reveals a startling proportion of colocalized cell- and context-specific TF-binding patterns, implying TF interactions play a critical role in transcription. These interactions depend on the chromatin architecture, that predominantly acts to predetermine accessibility of TF-binding sites at regulatory elements. Here, we summarize recent findings that highlight the importance of combinatorial TF interactions in determining diverse nuclear receptor-mediated transcriptional responses, emphasizing the significance of chromatin structure in directing TF and nuclear receptor recruitment. Interactions between TFs are likely to be a general mechanism of regulatory factors, contributing to transcriptional control in health and disease.
authors: Henry Wellcome Laboratories for Integrative Neuroscience & Endocrinology, Faculty of Medicine & Dentistry, University of Bristol, Bristol, BS1 3NY, UK.
authors: Charlotte L
authors: CL
authors: George
authors: Stafford L
authors: SL
authors: Lightman
authors: Simon C
authors: SC
authors: Biddie
mesh_terms: D002843:Chromatin / Q000235:genetics* / Q000502:physiology; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D023281:Genomics / Q000379:methods; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D008954:Models, Biological; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D002843:Chromatin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors