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Identification of a retinoic acid responsive element in the retinoic acid receptor & beta;gene

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Abstract

RETINOIC acid, the first morphogen described so far in verteá-brates, is a vitamin A derivative which exerts striking effects on development and differentiation1–3. The identification of three retinoic acid receptors as members of the nuclear receptor super-family provides an explanation for the molecular action of morphogens on gene expression4–8. Functional analysis of the receptors requires the identification of target genes and of their cis-acting retinoic acid-responsive elements. We have previously shown that the retinoic acid receptor β gene is transcriptionally up-regulated by retinoic acid9 and now report the characterization of a functional retinoic acid responsive element in the β gene that mediates trans-activation by retinoic acid. Using deletion mapping, we have identified a 27-base pair fragment, located 59 base pairs upstream of the transcriptional start, which confers retinoic acid responsiveness on the herpes virus thymidine kinase promoter. This sequence contains a perfect direct repeat of the motif GTTCAC, which is reminiscent of the 5′ half-palindrome of the thyroid and oestrogen hormone responsive elements. Specific binding of the p protein to the retinoic acid responsive element is demonstrated and is independent of the presence of retinoic acid. Both α and β receptors enhance retinoic acid response in CV1 cells, indicating that they can both act through the same DNA sequence.

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Author notes

  1. Maria del Mar Vivanco-Ruiz and Henk Stunnenberg: European Molecular Biology Laboratory, Meyerhofstrasse 1, 6900 Heidelberg, FRG

Authors and Affiliations

  1. Unite de recombinaison et d'expression genetique (INSERM U 163, CNRS UA 271), Institut Pasteur, 28 rue du Dr Roux, 75724, Paris, Cedex 15, France

    Hugues de The, Maria del Mar Vivanco-Ruiz, Pierre Tiollais, Henk Stunnenberg & Anne Dejean

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  1. Hugues de The
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  2. Maria del Mar Vivanco-Ruiz
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  3. Pierre Tiollais
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  4. Henk Stunnenberg
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  5. Anne Dejean
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de The, H., del Mar Vivanco-Ruiz, M., Tiollais, P. et al. Identification of a retinoic acid responsive element in the retinoic acid receptor & beta;gene. Nature 343, 177–180 (1990). https://doi.org/10.1038/343177a0

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  • DOI: https://doi.org/10.1038/343177a0

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