The promoter context is a decisive factor in establishing selective responsiveness to nuclear class II receptors

The EMBO Journal
M V SanguedolceH G Stunnenberg

Abstract

The vigorous retinoic acid (RA)-dependent activation of the retinoic acid receptor beta2 (RARbeta2) gene in embryonal carcinoma (EC) cells is mediated by retinoid receptor heterodimers (RXR-RAR) binding to RAREs that are closely positioned to the TATA box and an EC cell-specific co-factor activity termed E1A-LA. Using a series of direct repeat (DR) elements, we now show that positioning RXR-RAR in close proximity to the basal transcription machinery assembled on the TATA box is decisive in RA responsiveness in EC cells. Notably, a DR1 element functions predominantly as an RAR-responsive element when placed in the context of the RARbeta2 promoter. Moreover, DR3 and DR4 elements which mediate vitamin D3 and thyroid hormone responses, respectively, in other contexts, are converted to exclusive RAR response elements when placed in the RARbeta2 promoter and EC cell context. In differentiated cells, the adenovirus E1A(13S) protein is required to achieve high level RA activation through all of the different DR elements placed in the RARbeta2 context, suggesting that the molecular bridging function of E1A-LA [E1A(13S)] is essential to redefining response element specificity. Finally, we show that the arrangement of cis-acting elements ...Continue Reading

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Citations

Mar 4, 2009·Proceedings of the National Academy of Sciences of the United States of America·Bénédicte MascrezManuel Mark
Aug 3, 2010·Trends in Endocrinology and Metabolism : TEM·Philippe LefebvreBart Staels
Feb 27, 2003·Journal of Neurochemistry·Subbiah PugazhenthiJane E-B Reusch
Feb 25, 2005·Vitamins and Hormones·Philippe LefebvreBruno Lefebvre
Oct 12, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G SolanesF Villarroya
Feb 7, 2001·Journal of Neurochemistry·J M Cosgaya, A Aranda

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