Transcription factors nuclear hormone receptor

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 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. 

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). 

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]. 

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. 

Nuclear hormone receptors comprise a gene superfamily encoding for transcription factors that transfer endogenous (e.g., small, lipophilic hormones)... 

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],... 

Peroxisome proliferator activated receptors (PPARs) are members of the nuclear hormone receptors superfamily of ligand-activated transcription factors that are related to retinoid, steroid and thyroid receptors. All members of this superfamily have a similar structure the amino-terminal region allows ligand-independent activation, confers con-... 

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