Epigenetic regulation of retinoic acid-producing capacity of dendritic cells depending on their lineages

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Retinoic acid (RA)-producing dendritic cells (DC) are present in the gut-related tissue, and play important roles in the gut immunity. ALDH1A2 is the key enzyme for producing RA in these DC. The Aldh1a2 promoter region was GC-rich, and contained an Sp1-binding site and an RA response element (RARE) half-site near the TATA box. Among various animal species, the sequences of this region were well conserved. Sp1 and the RA receptor (RAR)/retinoid X receptor (RXR) heterodimer mutually enhanced their binding to these sites and cooperatively enhanced the promoter activity in the presence of RA. Accordingly, RA is an essential co-factor for inducing ALDH1A2 expression in DC. DNA methylation in the Aldh1a2 promoter region inhibited its activation. However, in normal DC subsets and other immune cells, the epigenetic regulation by Sp1 or histone acetylation but not DNA methylation appeared to participate in the regulation of RALDH2 gene expression.