Changes in Attitude, Changes in Latitude: Nuclear Receptors Remodeling Chromatin to Regulate Transcription

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate important physiological processes. To activate or repress genes assembled naturally as chromatin, NRs recruit two distinct enzymatic activities, namely histone-modifying enzymes and ATP-dependent chromatin remodeling complexes, to alter local chromatin structure at target gene promoters. In this review, we examine the functional relationship between ATP-dependent chromatin remodeling complexes and NRs in the context of transcriptional regulation. Using the steroid-responsive mouse mammary tumor virus promoter as a model system, we discuss in detail the molecular mechanisms underlying the recruitment of these complexes and subsequent chromatin structure changes catalyzed by this group of enzymes. In addition, we extend the discussion to other NR-regulated promoters including the pS2 promoter. Finally, we summarize specific principles governing this critical relationship, identify unanswered questions and discuss the potential application of these principles in rational drug design.