DNA-looping by RXR tetramers permits transcriptional regulation "at a distance".
J Mol Biol
; 343(2): 327-38, 2004 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-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.
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Bases de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Transcrição Gênica
/
DNA
/
Regulação da Expressão Gênica
/
Receptores do Ácido Retinoico
/
Estrutura Quaternária de Proteína
/
Conformação de Ácido Nucleico
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Mol Biol
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos