Retinoic acid receptors (RARs) are members of the nuclear receptor (NR) superfamily of ligand-dependent transcription factors. Three family members exist, alpha, beta and gamma, each gene being expressed into several isomers that vary in their N-terminus. RARs share the common nuclear receptor organization in several regions of homology, corresponding to different functional domains ^[1]. The N-terminal A/B region contains the AF-1 transactivation domain, which functions independently of ligand binding. The DNA binding domain, a type-II zinc finger motif, is located in region C. Finally, the D/E/F regions contain the ligand-binding domain and a second transactivation domain, AF-2, which functions in a ligand-dependent fashion.

RARs bind DNA as heterodimers with members of another family of NRs, the retinoid X receptors (RXRs). RAR/RXR heterodimers bind specific retinoic acid response elements (RAREs), usually composed of two or more repeats of the motif PuG(G/T)TCA arranged as direct repeats but also inverted or everted repeats ^[2]. In the absence of the ligand retinoic acid (RA), the RAR/RXR heterodimers are bound to the DNA and repress transcription through recruitment of corepressors such as NCoR or SMRT. Ligand binding induces a conformational change that allows for the dissociation of corepressors and the recruitment of coactivators^[3][4].

RARs control gene pathways that play important roles during development and cell differentiation through direct DNA binding, but also through tethering to DNA via protein-protein interactions with other transcription factors and through non-genomic mechanisms of action ^[5][6].