Polarity-specific activities of retinoic acid receptors determined by a co-repressor.
1995 (English)In: Nature, ISSN 0028-0836, Vol. 377, no 6548, 451-454 p.Article in journal (Refereed) Published
Retinoic acid receptors (RARs) and retinoid-X receptors (RXRs) activate or repress transcription by binding as heterodimers to DNA-response elements that generally consist of two direct repeat half-sites of consensus sequence AGGTCA. On response elements consisting of direct repeats spaced by five base pairs (DR + 5 elements), RAR/RXR heterodimers activate transcription in response to RAR-specific ligands, such as all-trans-retinoic acid (RA). In contrast, on elements consisting of direct repeats spaced by one base pair (DR + 1 elements), RAR/RXR heterodimers exhibit little or no response to activating ligands and repress RXR-dependent transcription. Here we show that ligand-dependent transactivation by RAR on DR + 5 elements requires the dissociation of a new nuclear receptor co-repressor, N-CoR, and recruitment of the putative co-activators p140 and p160. Surprisingly, on DR + 1 elements, N-CoR remains associated with RAR/RXR heterodimers even in the presence of RAR ligands, resulting in constitutive repression. These observations indicate that DNA-response elements can allosterically regulate RAR-co-repressor interactions to determine positive or negative regulation of gene expression.
Place, publisher, year, edition, pages
Nature Publishing Group, 1995. Vol. 377, no 6548, 451-454 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-87599DOI: 10.1038/377451a0ISI: A1995RY19000056PubMedID: 7566126OAI: oai:DiVA.org:liu-87599DiVA: diva2:589566