Retinoic acid receptors recognise the mouse genome through binding elements with diverse spacing and topology

[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.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Moutier, Emmanuel

Ye, Tao

Choukrallah, Mohamed-Amin

Urban, Sylvia

Osz, Judith

Chatagnon, Amandine

Delacroix, Laurence ; Université de Liège - ULiège > Département des sciences cliniques > GIGA-R: Neurobiologie du développement

Langer, Diana

Rochel, Natacha

Moras, Dino

Benoit, Gérard

Davidson, Irwin

Language :

English

Title :

Retinoic acid receptors recognise the mouse genome through binding elements with diverse spacing and topology

Publication date :

01 June 2012

Journal title :

Journal of Biological Chemistry

ISSN :

0021-9258

eISSN :

1083-351X

Publisher :

American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 24 June 2012

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