Intersection of nuclear receptors and the proteasome on the epigenetic landscape

Nuclear receptors (NRs) represent a class of transcription factors that associate with both positive and negative chromatin modifying complexes to activate or repress gene transcription. The 26S proteasome plays a major role in NR-regulated gene transcription by tightly regulating the levels of the receptor and coregulator complexes. Recent evidence suggests a robust nonproteolytic role for specific proteasome subunits in gene transcription mediated via alterations in specific histone modifications. The involvement of nuclear receptors and the proteasome with chromatin modifying complexes or proteins, particularly those that modify DNA and histone proteins, provides an opportunity to review two critical epigenetic mechanisms that control gene expression and heritable biological processes. Both nuclear receptors and the proteasome are targets of environmental factors including some which lead to epigenetic changes that can influence human diseases such as cancer. In this review, we will explore molecular mechanisms by which NR-mediated gene expression, under the control of the proteasome, can result in altered epigenetic landscapes.