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Relocalization of retinoic acid receptors from non-canonical to canonical spaced binding elements during embryoid body differentiation


ABSTRACT: Retinoic Acid Receptors (RARs) bind RA-response elements in regulatory regions of their target genes. While canonical RAREs comprise direct repeats of the consensus 5’-RGKTCA-3’ sequence separated by 1, 2 or 5 nucleotides (DR1, DR2, DR5), we show that shortly after RA treatement of mouse embryoid bodies or F9 cells, RARs occupy a large repertoire of DR0, DR2, DR5, DR8 and IR0 elements. In vitro, RAR-RXR bind these non-canonical spacings 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 and acts as an RARE. At later stages of embryoid body differentiation, RARs relocalise to a restricted repertoire of sites comprising predominantly DR5 elements. Differentiation thus involves genomic relocalisation of RARs, and a switch from DR0 and DR8 at early times to DR5 at later stages. Examination of genomic localisation of RAR in differentiating embryoid bodies.

ORGANISM(S): Mus musculus

SUBMITTER: Tao YE 

PROVIDER: E-GEOD-35599 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Moutier Emmanuel E   Ye Tao T   Choukrallah Mohamed-Amin MA   Urban Sylvia S   Osz Judit J   Chatagnon Amandine A   Delacroix Laurence L   Langer Diana D   Rochel Natacha N   Moras Dino D   Benoit Gerard G   Davidson Irwin I  

The Journal of biological chemistry 20120601 31


Retinoic acid receptors (RARs) heterodimerize with retinoid X receptors (RXRs) and bind to RA response elements (RAREs) in the regulatory regions of their target genes. Although 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  ...[more]

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