p27(Kip1) directly represses Sox2 during embryonic stem cell differentiation.
Cell Stem Cell
; 11(6): 845-52, 2012 Dec 07.
Article
em En
| MEDLINE
| ID: mdl-23217425
ABSTRACT
The mechanisms responsible for the transcriptional silencing of pluripotency genes in differentiated cells are poorly understood. We have observed that cells lacking the tumor suppressor p27 can be reprogrammed into induced pluripotent stem cells (iPSCs) in the absence of ectopic Sox2. Interestingly, cells and tissues from p27 null mice, including brain, lung, and retina, present an elevated basal expression of Sox2, suggesting that p27 contributes to the repression of Sox2. Furthermore, p27 null iPSCs fail to fully repress Sox2 upon differentiation. Mechanistically, we have found that upon differentiation p27 associates to the SRR2 enhancer of the Sox2 gene together with a p130-E2F4-SIN3A repressive complex. Finally, Sox2 haploinsufficiency genetically rescues some of the phenotypes characteristic of p27 null mice, including gigantism, pituitary hyperplasia, pituitary tumors, and retinal defects. Collectively, these results demonstrate an unprecedented connection between p27 and Sox2 relevant for reprogramming and cancer and for understanding human pathologies associated with p27 germline mutations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Diferenciação Celular
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Inibidor de Quinase Dependente de Ciclina p27
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Células-Tronco Embrionárias
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Fatores de Transcrição SOXB1
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell Stem Cell
Ano de publicação:
2012
Tipo de documento:
Article