Transcription factors nuclear receptor superfamily

Peroxisome Proliferator-Activated Receptors. Figure 1 Common structural and functional features of nuclear receptor transcription factors. Consistent with other members of the nuclear receptor superfamily, the PPARs have a modular domain structure consisting of domains A/B, C, D, and E. Each domain is associated with specific functions. 

Figure 43-11. The hormone response transcription unit. The hormone response transcription unit is an assembly of DNA elements and bound proteins that interact, through protein-protein interactions, with a number of coactivator or corepressor molecules. An essential component is the hormone response element which binds the ligand (A)-bound receptor (R). Also Important are the accessory factor elements (AFEs) with bound transcription factors. More than two dozen of these accessory factors (AFs), which are often members of the nuclear receptor superfamily, have been linked to hormone effects on transcription. The AFs can interact with each other, with the liganded nuclear receptors, or with coregulators. These components communicate with the basal transcription complex through a coregulator complex that can consist of one or more members of the pi 60, corepressor, mediator-related, or CBP/p300 families (see Table 43-6).

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. 

In addition to SREBPs, several members of the nuclear receptor superfamily regulate lipid metabolism. Nuclear receptors are transcription factors that are generally activated when bound to specific small-molecule ligands (Chapter 11). Certain nuclear receptors influence whole-body lipid metabolism by regulating the absorption of dietary lipids, cellular synthesis of lipids, transport protein-mediated import and export of lipids, levels of lipoproteins and their receptors, and catabolism of lipids (e.g., fatty acid oxidation in the peroxisome) and their secretion from the body. 

Several transcription factor-binding sites have been mapped in the CYP7A1 gene promoter, and most of these bind transcription factors that are members of the nuclear receptor superfamily (Table 2). Some of these receptors, notably the liver X receptor a (LXRa NR1H3) and peroxisome proliferator-activated receptor a (PPARa NRICI), bind to their target elements as heterodimers with retinoid X receptor a (RXRa NR2B1). 

The progesterone receptor is a ligand-activated transcription factor and a member of the nuclear receptor superfamily. All nuclear receptors have three conserved functional domains, including the DNA binding domain, the N-terminal domain, and the C-terminal... 

Nuclear receptors (NRs) are members of a large superfamily of evolutionarily related DNA-binding transcription factors that regulate programs involved in a broad spectrum of physiological phenomena. 

While bound to its cognate response element, the liganded/dimerized receptor recruits co-activator proteins that link with additional transcription factors, often leading to acetylation of histones, which opens up the nucleo-some to admit RNA polymerase II to the transcription start site. As would be expected, given that there is a sizeable superfamily of nuclear receptors and numerous interacting proteins, this simplified central theme is subject to many variations and complexities that allow subtle fine-tuning of regulatory responses. 

---