Glucocorticoid receptor-mediated chromatin remodeling in vivo

Abstract

The compaction of DNA into chromatin provides an additional level of gene regulation in eukaryotes that may not be available to prokaryotes. When packaged as chromatin, most promoters are transcriptionally repressed, and transcription factors have reduced access to their binding sites. The glucocorticoid receptor (GR) is a ligand-activated transcription factor that regulates the activity of genes involved in many physiological processes. To regulate eukaryotic genes, the GR binds to target sites within promoter regions of genes assembled as chromatin. This interaction alters the nucleosomal architecture to allow binding of other transcription factors, and formation of the preinitiation complex. The mouse mammary tumor virus (MMTV) promoter has been used extensively as a model to explore the processes by which the GR remodels chromatin and activates transcription. Significant progress has been made in our understanding of the mechanisms used by the GR to modify chromatin structure, and the limits placed on the GR by post-translational modifications of histones. We will describe recent developments in the processes used by the GR to activate transcription in vivo via chromatin remodeling complexes, histone H1 phosphorylation, and recruitment of diverse coactivators.