ORBi: Moutier Emmanuel - Retinoic acid receptors recognise the mouse genome through binding elements with diverse spacing and topology

Reference : Retinoic acid receptors recognise the mouse genome through binding elements with diverse...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/2268/126019

Title :	Retinoic acid receptors recognise the mouse genome through binding elements with diverse spacing and topology
Language :	English
Author, co-author :	Moutier, Emmanuel [ > > ]
	Ye, Tao [ > > ]
	Choukrallah, Mohamed-Amin [ > > ]
	Urban, Sylvia [ > > ]
	Osz, Judith [ > > ]
	Chatagnon, Amandine [ > > ]
	Delacroix, Laurence [Université de Liège - ULg > Département des sciences cliniques > GIGA-R: Neurobiologie du développement > >]
	Langer, Diana [ > > ]
	Rochel, Natacha [ > > ]
	Moras, Dino [ > > ]
	Benoit, Gérard [ > > ]
	Davidson, Irwin [ > > ]
Publication date :	1-Jun-2012
Journal title :	Journal of Biological Chemistry
Publisher :	American Society for Biochemistry and Molecular Biology
Audience :	International
ISSN :	0021-9258
e-ISSN :	1083-351X
City :	Baltimore
Country :	MD
Keywords :	[en] retinoic acid receptors ; DNA binding ; transcriptional activation
Abstract :	[en] Retinoic Acid Receptors (RARs) heterodimerise with Retinoid X Receptors (RXRs) and bind to RA-response elements (RAREs) in the regulatory regions of their target genes. While previous studies on limited sets of RA-regulated genes have defined canonical RAREs as direct repeats of the consensus RGKTCA separated by 1, 2 or 5 nucleotides (DR1, DR2, DR5), we show that in mouse embryoid bodies or F9 embryonal carcinoma cells, RARs occupy a large repertoire of sites with DR0, DR8 and IR0 (inverted repeat 0) elements. Recombinant RAR-RXR binds these non-canonical spacings in vitro with comparable affinities to DR2 and DR5. Most DR8 elements comprise three half sites with DR2 and DR0 spacings. This specific half site organisation constitutes a previously unrecognised, but frequent signature of RAR binding elements. In functional assays, DR8 and IR0 elements act as independent RAREs, while DR0 does not. Our results reveal an unexpected diversity in the spacing and topology of binding elements for the RAR-RXR heterodimer. The differential ability of RAR-RXR bound to DR0 compared to DR2, DR5 and DR8 to mediate RA-dependent transcriptional activation indicates that half site spacing allosterically regulates RAR function.
Target :	Researchers
Permalink :	http://hdl.handle.net/2268/126019

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