Retinoic acid, gene transcription regulated

Dietary carotenes and carotenoids are absorbed and transported in the plasma of humans and animals by lipoproteins.149 Tire conversion of carotenes to vitamin A (Box 22-A) provides the aldehyde retinal for synthesis of visual pigments (Chapter 23) and retinoic acid, an important regulator of gene transcription and development (Chapter 32).150 152c See also Section E,5. 

Jarrous N, Kaempfer R (1994) Induction of human interleukin-1 gene expression by retinoic acid and its regulation at processing of precursor transcripts. J Biol Chem 269 23 141-23 149... 

A most important function of vitamin A is in the control of cell differentiation and mrnover. PsA-trans-retinoic acid and 9-cw-retinoic acid (Figure 45-1) regulate growth, development, and tissue differentiation they have different actions in different tissues. Like the steroid hormones and vitamin D, retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific genes. There are two families of nuclear retinoid receptors the retinoic acid receptors (RARs) bind all-rrijw-retinoic acid or 9-c -retinoic acid, and the retinoid X receptors (RXRs) bind 9-cw-retinoic acid. 

Lipophilic signaling substances include the steroid hormones, calcitriol, the iodothy-ronines (T3 and T4), and retinoic acid. These hormones mainly act in the nucleus of the target cells, where they regulate gene transcription in collaboration with their receptors and with the support of additional proteins (known as coactivators and mediators see p.244). There are several effects of steroid hormones that are not mediated by transcription control. These alternative pathways for steroid effects have not yet been fully explained. 

The heterotypic dimerization significantly expands the repertoire for tissue-specific regulation of transcription activity. The tissue-specific expression of a particular pattern of transcriptional activators can be used to select only certain DNA-binding elements out of a series of similar elements, and thus to specifically induce certain genes. This strategy is extensively used by the receptors for retinoic acid (see chapter 4). 

Figure 29-6. Gene transcription is regulated by retinoic acid.Ah-Zrwm-retinoic acid and 9-cA-retinoic acid are ligands for retinoic acid receptors (RARs) and retinoid X receptors (RXRs), respectively. The RXRs can form heterodimers with RARs and with the thyroid hormone receptors (TRs), the vitamin D receptor (VDR), and the peroxisome proliferator-activated receptors (PPARs) and a number of other hormone- and nutrient-responsive transcription factors to moderate gene transcription. Because of the ability of RXR to form heterodimers with other nuclear receptors, vitamin A has abroad effect on many hormonally and nutrient-responsive genes.

Glass, C. K, Lipkin, S. M., Devary, 0. V, and Rosenfeld, M. G. (1989). Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer, Cell 59, 697-708,... 

The hormonal forms of vitamin A are all-frans-retinoic acid and 9-cfs-retinoic acid. The hormonal form of vitamin D is 1,25-dihydroxyvitamin D3, and that of thyroid hormone is T3. These hormones act within the nucleus, where they bind to special proteins. These proteins are classed as transcription factors. Various transcription factors bind to the regulatory regions of all genes and influence the rate of transcription (Figure 9.60). Many genes are continuously transcribed, and here the term "basal level of transcription" is used to describe the rate of transcription. In cases where the gene is regulated, special transcription factors are used to enhance or inhibit the basal level of transcription. 

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