Chapter 6 Chromatin Remodeling and Nuclear Receptor Signaling

Nuclear receptors (NRs) constitute a large family of ligand-dependent transcription factors that play key roles in development, differentiation, metabolism, and homeostasis. They participate in these processes by coordinating and regulating the expression of their target genes. The eukaryotic genome is packaged as chromatin and is generally inhibitory to the process of transcription. NRs overcome this barrier by recruiting two classes of chromatin remodelers, histone modifying enzymes and ATP-dependent chromatin remodelers. These remodelers alter chromatin structure at target gene promoters by posttranslational modification of histone tails and by disrupting DNA-histone interactions, respectively. In the presence of ligand, NRs promote transcription by recruiting remodeling enzymes that increase promoter accessibility to the basal transcription machinery. In the absence of ligand a subset of NRs recruit remodelers that establish and maintain a closed chromatin environment, to ensure efficient gene silencing. This chapter reviews the chromatin remodeling enzymes associated with NR gene control, with an emphasis on the mechanisms of NR-mediated repression.