pRetinoic acid is a signalling molecule central to morphogenesis and musculoskeletal development. It can exist in several isomeric forms, of which all-itrans/i- and 9-icis/i-retinoic acid are thought to be the most relevant as signalling molecules. Retinoic acid regulates gene expression via RARs (retinoic acid receptors) working as heterodimers with RXRs (retinoid X receptors). RXRs also heterodimerize with other nuclear receptors. In this issue of the iBiochemical Journal/i, Harris et al. have shown that an enhancer responsible for chondrocyte-specific expression of the icol11a2/i gene is itself regulated by a retinoic-acid-dependent interaction with RXRβ bound to a downstream response element. Thus, RXRs bound to hormone-response elements can regulate gene expression indirectly via interactions with tissue-specific enhancers. This study raises interesting questions about the nature of the response element, the RXRβ partner and the ligands able to influence icol11a2/i expression, and will provide a model system with which to understand tissue and ligand specificity of retinoid responses./p
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