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Title: DNA-looping by RXR tetramers permits transcriptional regulation "at a distance". Author: Yasmin R, Yeung KT, Chung RH, Gaczynska ME, Osmulski PA, Noy N. Journal: J Mol Biol; 2004 Oct 15; 343(2):327-38. PubMed ID: 15451664. Abstract: RXR, a member of the superfamily of nuclear hormone receptors, regulates gene transcription in response to 9-cis-retinoic acid. We previously showed that, among nuclear receptors, RXR is unique in that it self-associates into homotetramers, and that these tetramers dissociate rapidly upon ligation. Here, we report that binding of RXR tetramers to DNA containing two RXR response elements results in a dramatic DNA-looping. RXR can thus juxtapose distant DNA sequences, enabling transcriptional regulation by far-upstream factors. We show that RXR functions as a DNA architectural factor and that, while this activity is regulated by 9-cis-retinoic acid, it is distinct from and independent of the receptor's intrinsic transcriptional activity. The data establish RXR as the first identified architectural factor whose activity is regulated by a small ligand, and demonstrate a novel mechanism of transcriptional regulation by retinoids.[Abstract] [Full Text] [Related] [New Search]