Nuclear Receptor Recruitment of Histone-Modifying Enzymes to Target Gene Promoters

Abstract

Nuclear receptors (NRs) compose one of the largest known families of eukaryotic transcription factors and, as such, serve as a paradigm for understanding the fundamental molecular mechanisms of eukaryotic transcriptional regulation. The packaging of eukaryotic genomic DNA into a higher ordered chromatin structure, which generally acts as a barrier to transcription by inhibiting transcription factor accessibility, has a major influence on the mechanisms by which NRs activate or repress gene expression. A major breakthrough in the field's understanding of these mechanisms comes from the recent identification of NR-associated coregulatory factors (i.e., coactivators and corepressors). Although several of these NR cofactors are involved in chromatin remodeling and facilitating the recruitment of the basal transcription machinery, the focus of this chapter is on NR coactivators and corepressors that act to covalently modify the amino-terminal tails of core histones. These modifications (acetylation, methylation, and phosphorylation) are thought to directly affect chromatin structure and?or serve as binding surfaces for other coregulatory proteins. This chapter presents the most current models for NR recruitment of histone-modifying enzymes and then summarizes their functional importance in NR-associated gene expression.