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Cancer Center, La Jolla Cancer Research Foundation La Jolla, California 92037
Address requests for reprints to: Magnus Pfahl, Ph.D., 10901 North Torrey Pines Road, La Jolla, California 92037.
Abstract
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 RAR
is a poor activator of this RARE. However, the response element is bound with high affinity by both RARβ and RAR as well as by thyroid hormone receptors. Thus, interaction between specific response elements and receptors is insufficient for gene activation.
FOOTNOTES
This work was supported by NIH Grant DK-35083.
* Supported by a fellowship from the Deutsche Forschungs-gemeinschaft.
Received for publication June 20, 1990. Revision received August 8, 1990. Accepted for publication August 17, 1990.
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