Nuclear hormone receptors transcription

Figure 8 Schematic diagram of the nuclear hormone receptor transcription mechanism...

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. 

The antagonist-induced conformation of nuclear hormone receptors attracts co-repressors like Nco/SMRT (nuclear hormone receptor co-repressor/silencing mediator of retinoid and thyroid receptors) which further recruit other nuclear proteins with histone deacetylase activity. Their action leads to chromatin condensation, thus preventing the general transcription apparatus from binding to promoter regions. 

The nuclear receptor superfamily consists of a diverse set of transcription factors that were discovered because of a sequence similarity in their DNA-binding domains. This family, now with more than 50 members, includes the nuclear hormone receptors discussed above, a number of other receptors whose ligands were discovered after the receptors were identified, and many putative or orphan receptors for which a ligand has yet to be discovered. 

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... 

The zinc fingers are common structures among the transcription factors. Nevertheless, the coordination with zinc is more frequently produced between two histidine residues and two neighboring cysteines than when it is among four cysteine residues, as occurs in the nuclear hormone receptors. The zinc fingers provide an optimum architecture for the mutual recognition between specific sequences of amino acids and nucleotides. In the case of the nuclear receptors, the interaction occurs between particular amino acids of the DBD and guanine residues of the DNA sequence (Fig. 1.7). 

The final phase of action of the hormones that utilize nuclear hormone receptors lies in the modification of the gene transcription. In spite of the enormous... 

Nuclear hormone receptors comprise a family of mechanistically related transcription factors... 

Nuclear hormone receptors, including those for the principal classes of steroids, retinoids, vitamin D, and thyroid hormones, are transcription factors that influence gene expression. 

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]. 

In the absence of ligand, some nuclear hormone receptors associate with co-repressors, namely, SMRT (silencing mediator of retinoic acid and thyroid hormone receptors) and N-CoR (nuclear receptor co-repressor). Both, SMRT and N-CoR, recruit coregulatory protein SINS and histone deacetylases (HDACs) to form a large co-repressor complex that contains histone deacetylase activity, implicating histone deacetylation in transcriptional repression [52,53]. 

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...

Tontonoz, P, Graves, R. A., Budavari, A. I., Erdjument-Bromage, H., Lui, M., Hu, E., Tempst, P, and Spiegelman, B. M. (1994). Adipocyte-Specific Transcription Factor ARF6 Is a Heterodimeric Complex of Two Nuclear Hormone Receptors, PPAR Gamma and RXR Alpha. Nucleic Adds Res. 22, 5628-5634. 

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