Mechanisms of gene regulation by all trans retinoic acid. (A) RARs complex with their RXR heterodimer partner bind to retinoic acid response elements (RARE) DNA sequences. In the absence of atRA, they recruit corepressors that link RAR-RXR complex to histone deacetylases (HDACs), which leads to chromatin condensation and repression of gene expression. When atRA binds to RARs, a conformational change occurs which releases corepressors and recruits coactivators. The coactivators interact with histone acetylases (HATs) which lead to chromatin decompaction and allow access to DNA by transcriptional machinery (27, 28). (B) Example of genes that are regulated by RA (26). The genes shown have conserved RAREs (or predicted RAREs) in their promoters and the expression is regulated in a RA-dependent manner. RAR, retinoic acid receptor; RXR, rexinoid receptor; atRA, all trans retinoic acid.