Figure 2.

Canonical RA signaling activity occurs when RA regulates gene transcription by binding as ligand to RAR nuclear transcription factors at RARE sites. (A) RARs function as heterodimer with RXRs. Binding of RA (represented by orange hexagon) to the ligand-binding domain of a RAR heterodimerized with a RXR can activate transcription; (B) RAR–RXR heterodimers bind to DNA at RARE sites. Examples of classical RARE binding sites consist of two directly repeated hexamer motifs separated by spacer nucleotide sequences of different lengths. Examples of DR5, DR2, and DR1 RAREs from important RA-regulated developmental genes are shown.