Identification and characterization of a functional zebrafish smrt corepressor (ncor2)

The retinoic acid receptors (RARs or rars) and the thyroid hormone receptors are members of the steroid receptor superfamily that interact with their DNA response elements (for RARs: retinoic acid response elements or RAREs) in the regulatory regions of promoters in the absence of their ligand. In this ligand minus configuration, it has been suggested that the RAR provides a binding site for a corepressor (SMRT or N-CoR) that also brings in other proteins to repress the gene. In the presence of the ligand, the receptor goes through an allosteric change eliminating the corepressor binding site and providing a coactivator binding site. In this manuscript we describe the isolation of the zebrafish corepressor, smrt. We show that its association with the zebrafish rar aa is sensitive to retinoic acid and that the corepressor mRNA is present in 8 cell zebrafish embryos - a time at which the embryonic genome is not active. We suggest that this rar-corepressor complex may be part of an embryonic, epigenetic switch that keeps retinoic acid responsive genes off before retinoic becomes available to the embryo.