Genome-wide mechanisms of nuclear receptor action.
Nuclear receptors are involved in a myriad of physiological processes, responding to ligands and binding to DNA at sequence-specific cis-regulatory elements. This binding occurs in the context of chromatin, a critical factor in regulating eukaryotic transcription. Recent high-throughput assays have examined nuclear receptor action genome-wide, advancing our understanding of receptor binding to regulatory elements. Here, we discuss current knowledge of genome-wide response element occupancy by receptors and the function of transcription factor networks in regulating nuclear receptor action. We highlight emerging roles for the epigenome, chromatin remodeling, histone modification, histone variants and long-range chromosomal interactions in nuclear receptor binding and receptor-dependent gene regulation. These mechanisms contribute importantly to the action of nuclear receptors in health and disease.
Laboratory of Receptor Biology and Gene Expression, Building 41, Room B602, 41 Library Dr., National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5055, USA.
Simon C
SC
Biddie
Sam
S
John
Gordon L
GL
Hager
D000818:Animals; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000378:metabolism; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000502:physiology*; D050436:Regulatory Elements, Transcriptional
D004268:DNA-Binding Proteins; D006657:Histones; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear