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Cooperativity of the glucocorticoid receptor and the CACCC-box binding factor

Nature volume 332, pages 87–90 (1988)Cite this article

Abstract

Glucocorticoid receptor binding sites (GRE) are often tightly clustered with other transcription factor binding sequences. Examples of this occur upstream of the genes for chicken lysozyme1,2 and human metallothionein IIA (ref. 3), in several retroviral LTRs4–6 and upstream of the rat tryptophan oxygenase (TO) gene7. In the TO gene, sequences immediately upstream of a glucocorticoid receptor binding site are required for steroid induction7 and contain a CACCC-box identical to that found in the β globin gene. Here we demonstrate specific binding to this TO-CACCC element and show that it will also act cooperatively with a MMTV glucocorticoid receptor binding site. The response to dexamethasone is independent of the order and relative orienta-tion of these elements but does depend on their precise spacing. Optimal induction occurs at a periodicity of approximately 10 base pairs (bp) indicating a requirement for stereospecific align-ment. Binding to the CACCC box, however, is not affected by its distance from the glucocorticoid receptor site. We conclude that the observed cooperativity is mediated by protein: protein intera-tions and does not depend on cooperative DNA binding.

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Authors and Affiliations

  1. Max-Planck-Institut für Biochemie, Genzentrum, D 8033, Martinsried, FRG

    Roland Schüle, Marc Muller, Hidetsugu Otsuka-Murakami & Rainer Renkawitz

  2. Department of Biochemistry, Aichi Medical University, Nagakute, Aichi, 480-11, Japan

    Hidetsugu Otsuka-Murakami

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  1. Roland Schüle
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  2. Marc Muller
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  3. Hidetsugu Otsuka-Murakami
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  4. Rainer Renkawitz
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Schüle, R., Muller, M., Otsuka-Murakami, H. et al. Cooperativity of the glucocorticoid receptor and the CACCC-box binding factor. Nature 332, 87–90 (1988). https://doi.org/10.1038/332087a0

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