Homo- and heterodimers of the retinoid X receptor (RXR) activate transcription in yeast (original) (raw)

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Laboratoire de Génétique Moléculaire des Eucaryotes du Centre National de la Recherche Scientifique, Unité 184 de Biologie Moléculaire et de Génie Génétique de I'lnstitut National de la Santé et de la Recherche Médicale, Institut de Chimie Biologique

11 rue Humann, 67085 Strasbourg Cedex, France

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Laboratoire de Génétique Moléculaire des Eucaryotes du Centre National de la Recherche Scientifique, Unité 184 de Biologie Moléculaire et de Génie Génétique de I'lnstitut National de la Santé et de la Recherche Médicale, Institut de Chimie Biologique

11 rue Humann, 67085 Strasbourg Cedex, France

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Laboratoire de Génétique Moléculaire des Eucaryotes du Centre National de la Recherche Scientifique, Unité 184 de Biologie Moléculaire et de Génie Génétique de I'lnstitut National de la Santé et de la Recherche Médicale, Institut de Chimie Biologique

11 rue Humann, 67085 Strasbourg Cedex, France

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Laboratoire de Génétique Moléculaire des Eucaryotes du Centre National de la Recherche Scientifique, Unité 184 de Biologie Moléculaire et de Génie Génétique de I'lnstitut National de la Santé et de la Recherche Médicale, Institut de Chimie Biologique

11 rue Humann, 67085 Strasbourg Cedex, France

*To whom correspondence should be addressed

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Laboratoire de Génétique Moléculaire des Eucaryotes du Centre National de la Recherche Scientifique, Unité 184 de Biologie Moléculaire et de Génie Génétique de I'lnstitut National de la Santé et de la Recherche Médicale, Institut de Chimie Biologique

11 rue Humann, 67085 Strasbourg Cedex, France

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Received:

22 December 1993

Accepted:

31 January 1994

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David M. Heery, Benoit Pierrat, Hinrich Gronemeyer, Pierre Chambon, Régine Losson, Homo- and heterodimers of the retinoid X receptor (RXR) activate transcription in yeast, Nucleic Acids Research, Volume 22, Issue 5, 11 March 1994, Pages 726–731, https://doi.org/10.1093/nar/22.5.726
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Abstract

The polymorphic nature of sequences which act as retinoic acid response elements (RAREs and RXREs) in transactivatlon assays In mammallan cells, suggests that elements consisting of a direct repetition of a half site motif, separated by 1 to 5 base pairs (DR1 to DR5), are targets for retinolc acid (RA) signalling. In a previous report we showed that in yeast cells, heterodimers of the retinoic acid receptors RARα and RXRα were required for efficient transcription of a reporter gene containing a DR5 element [Heery et al., (1993); Proc. Natl. Acad. Scl. USA, 90: 4281–4285]. Here we report that DR1 to DR5 elements containing a direct repeat of the 5′-AGGTCA-3′ motif, and an Inverted repeat of the same sequence with no spacer (IRO), behave as RAREs in yeast cells coexpressing RARα and RXRα, albeit with different efficacies. Heterodimer activity was strongest on a DR5 reporter gene, and the strength of activation of the reporter series (DR5 > DR1 > DR3 > DR2 = IRO = DR4) correlated with the ability of the heterodimer to bind to the corresponding sequences in vitro. Significantly, a reporter containing a DR1 element was selectively and efficiently activated In yeast cells expressing only RXRα. This activity was dependent on the Induction by 9-cls retinoic acid of an activation function (AF-2) located in the RXRα llgand binding domain. In addition, a strong synerglstlc activity of RXRa was observed on a reporter containing the putative RXR element (RXRE) from the rat CRBPII gene promoter. Thus, RXRα can function Independently as a transcription factor, in the absence of RARs or other heteromerlc partners. Similarly, homodimers of RARα selectively stimulated the transcription of a DR5 reporter in a ligand-dependent manner, but less efficiently than RARα/RXRα heterodimers.

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