Nuclear hormone receptors transcription regulation

Zhang, Y., Mangelsdorf, DJ. 2002. LuXuRies of lipid homeostasis the unity of nuclear hormone receptors, transcription regulation, and cholesterol sensing. Mol. Interv. 2 78-87. 

Once nuclear hormone receptors are bound to their hormone, they are capable of being integrated directly into the machinery that regulates the transcription of specific genes. This action is more direct, and apparently more... 

Nuclear receptors exert their different transcriptional functions through interactions with and the recruitment of co-factors to responsive promoters. Co-factors are either positive or negative regulatory proteins and are classified as co-activators, which promote, or co-repressors, which attenuate the activity of nuclear hormone receptors [46]. The molecular mechanisms that regulate the mutually exclusive interactions of the nuclear receptor with either class of co-factors have been analysed by crystallographic studies. Functional and structural studies have shown that co-activators interact with the transactivation function (AF) of nuclear hormone receptors via short, leucine-rich motifs (LXXLL) termed NR boxes , thereby transducing hormonal signals to the basal transcription machinery [47]. 

Fig. 4 Co-activator and co-repressor complexes are required for nuclear hormone receptor-mediated transcriptional regulation. The tissue-selective fine-tuning of gene transcription by nuclear hormone receptors is due to different co-regulatory complexes that have various functions and enzymatic activities. Co-activator complexes include factors that contain ATP-dependent chromatin remodelling activity often associated with histone acetyltransferase (HAT) activity. Co-repressors include ATP-dependent chromatin remodelling complexes, which function as platforms for the recruitment of several subcomplexes that often contain histone deacetylase (HDAC) activity...

The activation or inhibition of nuclear hormone receptors by synthetic androgens, with a readout (way) downstream of transcriptional regulation such as muscle growth or inhibition of sperm production (a highly educational example, isn t it). 

Nuclear Hormone Receptors Regulate Transcription by Recruiting Coactivators and Corepressors to the Transcription Complex... 

Katzenellenbogen JA, Katzenellenbogen BS. Nuclear hormone receptors Ligand-activated regulators of transcription and diverse cell responses. Chem Biol 1996 3 529-36. 

Nuclear hormone receptors (NRs) are ligand-activated transcription factors that regulate gene expression by interacting with hormone response elements on target genes (see also Chapter 12). This occurs via the formation of monomers, homodimers, or heterodimers generally with the retinoid X receptor (RXR) and interaction with the hormone response element [83,84],... 

Nuclear hormone receptors also include regions that interact with components ot the mediator complex. Thus, two mechanisms of gene regulation can work in concert. Modification of histones and chromatin remodeling can open up regions of chromatin into which the transcription complex can be recruited through protein- protein interactions. 

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