Small-Molecule Hormones: Molecular Mechanisms of Action
Figure 5
Coactivators, corepressors, chromatin, and regulation of transcription. (a) The coactivator complex consists of many proteins, including proteins with the LXXL (L: leucine, X: any amino acid) motif by which they bind to the hormone-activated nuclear receptor. Histone acetyltransferase activity might be presented by more than one protein of this complex. Decondensation of the chromatin structure upon histone acetylation and a direct interaction of the coactivator complex with basal transcription factors result in transcription activation. (b) In the absence of the hormone, receptor conformation promotes the binding of a multiprotein corepressor complex. Binding of the receptor to this complex occurs by the LXXI/HIXXXI/L (L: leucine, X: any amino acid, I: isoleucine, and H: histidine) motif present in a corepressor protein. The complex includes class I or class II histone deacetylase. Histone deacetylation leads to the condensation of chromatin and, as a result, limits the access of transcription factors to the DNA. As a result, transcription is inhibited. (c) Some corepressor proteins contain the LXXL motif and preferentially bind to the receptors activated by the hormone. Next, by the recruitment of the corepressor complex, including histone deacetylase, they stabilize tight chromatin structure and repress transcription. H: hormone, HR: nuclear hormone receptor, HRE: hormone response element, nHRE: negative hormone response element, CoA: corepressor complex, p160, p300/CBP, and p/CAF: coactivator proteins, LXXL: coactivator protein motif involved in receptor binding, HAT: histone acetyltransferase, CoR: corepressor complex, NCoR/SMRT: classic corepressor complexes, CoRNR: LXXI/HIXXXI/L corepressor protein motif involved in receptor binding, HDAC: histone deacetylase, RIP140/LCoR/Hr: nonclassical corepressor proteins preferentially binding to hormone-activated receptors, BTF: basal transcription factors, and RNA Pol II: type II RNA polymerase.
