Small-Molecule Hormones: Molecular Mechanisms of Action
Figure 4
Diagram of type II receptor genomic mode of action. (a) In the absence of the hormone, the receptor binds to HRE as heterodimer with 9-cis-retinoic acid receptor. The hormone-free receptor recruits a corepressor complex possessing a histone deacetylase activity. Deacetylation of histones results in chromatin condensation and in transcription inhibition. (b) In the circulation, the hormone forms complexes with transporting proteins. The hormone enters the cell by diffusion or is actively transported by specific cell membrane proteins. The majority of type II receptors reside in the nucleus. Upon hormone binding, the receptor changes its conformation, which results in the dissociation of the corepressor complex and in the binding of the coactivator complex. Histone acetylation by HDAC results in chromatin decondensation, which promotes transcription factor binding to DNA and transcription activation. H: hormone, RH: nuclear hormone receptor, RXR: 9-cis-retinoic acid receptor, HRE: hormone response element, CoA: coactivator complex, HAT: histone actyltransferase, CoR: corepressor complex, HDAC: histone deacetylase, TF: transcription factor, BTF: basal transcription factors, RNA Pol II: type II RNA polymerase, and R: ribosome.
