Ligand-dependent regulation of NR activity In the absence of agonist (red circles) or the presence of an antagonist (black circles) NR activity is inhibited by the recruitment of transcriptional CoRs. These CoRs repress gene transcription, in part by decreasing and increasing the levels of histone acetylation (yellow circles) and DNA methylation (orange circles), respectively. In contrast, agonists induce an exchange of CoRs by transcriptional CoAs, which induce an open conformation of the chromatin by promoting the opposite epigenetic modifications. Consequently, the recruitment of CoAs increases the transcriptional activity of NRs and, thus, gene transcription. HRE, hormone response element.