Lipid soluble vitamins in gene regulation

Vitamin A (retinol) and vitamin D are lipid soluble vitamins that are precursors of the nuclear hormones all‐trans retinoic acid (RA) and 1α,25‐dihydroxyvitamin D 3 (VD) that bind with high affinity to their cognate nuclear receptors, referred to as retinoic acid receptor (RAR) and vitamin D receptor (VDR). Both types of nuclear receptors are structurally related and belong to the same subclass of the nuclear receptor superfamily, a large family of ligand‐inducible transcription factors. Both RAR and VDR form heterodimers preferentially with the nuclear receptor for 9‐cis RA, referred to as the retinoid X receptor (RXR), but functional RAR‐VDR heterodimers have also been observed. Moreover, both types of nuclear receptors interact in a ligand‐dependent fashion with members of the same class of co‐activator, co‐repressor and co‐integrator proteins. These similar molecular mechanisms of action provide several possibilities for an interaction of RARs with VDR that are all based on allosteric protein—protein interactions. These interactions can result in either an additive or a transrepressive functional interference between RA and VD. The two remaining lipid soluble vitamins, vitamins E and K, are not known to interact with nuclear receptors, but their structure does not exclude this possibility. Moreover, for vitamin E modulatory effects on transcription factors, such as AP‐1, have been described. This review will discuss briefly gene regulation by the four lipid soluble vitamins.