The cell-cycle regulator geminin inhibits Hox function through direct and polycomb-mediated interactions.
Nature
; 427(6976): 749-53, 2004 Feb 19.
Article
em En
| MEDLINE
| ID: mdl-14973489
ABSTRACT
Embryonic development is tightly controlled. The clustered genes of the Hox family of homeobox proteins play an important part in regulating this development and also proliferation. They specify embryonic structures along the body axis, and are associated with normal and malignant cell growth. The cell-cycle regulator geminin controls replication by binding to the licensing factor Cdt1, and is involved in neural differentiation. Here, we show that murine geminin associates transiently with members of the Hox-repressing polycomb complex, with the chromatin of Hox regulatory DNA elements and with Hox proteins. Gain- and loss-of-function experiments in the chick neural tube demonstrate that geminin modulates the anterior boundary of Hoxb9 transcription, which suggests a polycomb-like activity for geminin. The interaction between geminin and Hox proteins prevents Hox proteins from binding to DNA, inhibits Hox-dependent transcriptional activation of reporter and endogenous downstream target genes, and displaces Cdt1 from its complex with geminin. By establishing competitive regulation, geminin functions as a coordinator of developmental and proliferative control.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Ciclo Celular
/
Proteínas de Homeodomínio
/
Regulação da Expressão Gênica no Desenvolvimento
/
Proteínas de Ciclo Celular
Limite:
Animals
Idioma:
En
Revista:
Nature
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Alemanha