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Nucleic Acids Research 2005 33(7):2269-2279; doi:10.1093/nar/gki503
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Published online 22 April 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

Article

The repressor DREAM acts as a transcriptional activator on Vitamin D and retinoic acid response elements

Sona Scsucova, Daniela Palacios, Magali Savignac1, Britt Mellström1, Jose Ramon Naranjo1 and Ana Aranda*

Instituto de Investigaciones Biomédicas ‘Alberto Sols’, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid Arturo Duperier 4, 28029 Madrid, Spain 1Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid Arturo Duperier 4, 28029 Madrid, Spain

*To whom correspondence should be addressed. Tel: +34 91 5854453; Fax: +34 91 5854401; Email: aaranda{at}iib.uam.es

Received February 19, 2005. Revised March 22, 2005. Accepted March 22, 2005.

DREAM (downstream regulatory element antagonist modulator) is a transcriptional repressor, which binds DREs (downstream response elements) in a Ca2+-regulated manner. The DREs consist of core GTCA motifs, very similar to binding motifs for non-steroid nuclear receptors. In this work, we find that DREAM stimulates basal and ligand-dependent activation of promoters containing vitamin D and retinoic acid response elements (VDREs and RAREs), consisting of direct repeats of the sequence AGT/GTCA spaced by 3 or 5 nt, respectively. Stimulation occurs when the element is located upstream, but not downstream, the transcription initiation site. Activation requires both Ca2+ binding to the EF-hands and the leucine-charged domains (LCDs), analogous to those responsible for the interaction of the nuclear receptors with coregulators. Further more, DREAM can bind both ‘in vitro’ and in chromatin immunoprecipitation assays to these elements. Importantly, ‘in vivo’ binding is only observed in vitamin D- or RA-treated cells. These results show that DREAM can function as an activator of transcription on certain promoters and demonstrate a novel role for DREAM acting as a potential modulator of genes containing binding sites for nuclear receptors.


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