Retinoic acid genomic expression

The specific role of vitamin A in tissue differentiation has been an active area of research. The current thinking, developed in 1979, involves initial dehvery of retinol by holo-B >V (retinol-binding protein) to the cell cytosol (66). Retinol is then ultimately oxidized to retinoic acid and binds to a specific cellular retinoid-binding protein and is transported to the nucleus. Retinoic acid is then transferred to a nuclear retinoic acid receptor (RAR), which enhances the expression of a specific region of the genome. Transcription occurs and new proteins appear during the retinoic acid-induced differentiation of cells (56). 

Apart from the effects on vision, most of the effects of vitamin A deficiency (Section 2.4) involve derangements of cell proliferation and differentiation (squamous metaplasia and keratinization of epithelia), dedifferentiation, and loss of ciliated epithelia. Retinoic acid has both a general role in growth and a specific morphogenic role in development and tissue differentiation. These functions are the result of genomic actions, modulating gene expression by activation of nuclear receptors. Both deficiency and excess of retinoic acid cause severe developmental abnormalities. 

Another set of binding proteins, specific for retinoic acid, is found in the nucleus of cells (13-15). Because they influence genome expression, they have been called retinoic acid receptors. Two families of these exist, the RAR family, which binds both eUl-trans and 9-cis retinoic acid, and the RXR family, which binds only 9-cis retinoic acid. These retinoic acid receptors belong to a superfamily of receptors, which also includes those for some steroids, tri-iodothyronine, and la,25-hydroxycholecalciferol (13-15). 

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