Figure 1.

(a) Cofactor exchange by heterodimeric nuclear hormone receptors. In the absence of ligands, these NRs are associated with corepressor complexes that possess HDAC activity and suppress the transcription of the target genes, which is called ligand-independent repression. When the ligands are present, corepressors dissociate, and coactivators are recruited instead. Many of these coactivators possess HAT activity. (b) Molecular action of homodimeric nuclear hormone receptors. In the absence of ligands, they bind to chaperone molecules, such as HSP 90 and HSP 70 in the cytosol. In addition, unliganded ER is also localized to the nucleus, but does not bind its target genes. Upon binding to the ligands, NRs enter nuclei, bind DNA, and stimulate transcription in association with coactivators. HSPs play important roles in nuclear translocation of NRs and transcriptional activity of liganded NRs. CoR, corepressor; CoA, coactivator; NR, nuclear hormone receptor; RXR, retinoid X receptor; Ac, acetylation; HSP, heat shock protein.