Regulated histone methyltransferase and demethylase complexes in the control of genes by nuclear receptors.

Liganded nuclear receptors (NRs) are DNA-binding transcription factors that control the transcription of target genes. Such NRs exert their transcriptional functions via ligand binding-induced interactions with a number of coregulator complexes to reorganize chromatin state. Intensive investigation of NR coregulator complexes has revealed that, besides histone acetylation, histone methylation is critical for ligand-dependent transcriptional controls by NRs. Our recent biochemical screening for NR coregulator complexes showed that the enzymatic activities of these histone methylation/demethylation complexes are under the control of posttranslational modifications (PTMs) of their catalytic subunit. Characterization of such regulated complexes has established the concept that transcriptional coregulator complexes sense and decode cellular signals at the molecular level. In this symposium review, we will illustrate our recent findings regarding PTM-based regulation of NR transcriptional control and discuss how these findings are applicable to the diverse roles of NR coregulators in interpreting regulatory signals into proper gene regulation.