A Retinoic Acid Receptor-Specific Element Controls the Retinoic Acid Receptor-β Promoter

The morphogen retinoic acid (RA) regulates gene transcription by interacting with specific nuclear receptors that recognize DNA sequences near responsive promoters. While much has recently been learned about the nuclear receptor proteins, little is known about the genes that are directly regulated by RA and their cis-acting response elements recognized by these receptors. Here we have analyzed the RA receptor-β (RARβ) gene promoter that is controlled by RA. We find that a RA-responsive element (RARE) is located adjacent to the TATA box. The RARE shows a direct repeat symmetry which is essential for its function. While thyroid hormone-responsive elements can also function as RAR response elements, we show here that this RARE is activated by endogenous RARs and RARβ, but cannot be regulated by thyroid hormone receptors and other known nuclear receptors. In addition, we find that RARγ is a poor activator of this RARE. However, the response element is bound with high affinity by both RARβ and RARγ as well as ...