Rif1 maintains telomere length homeostasis of ESCs by mediating heterochromatin silencing.
Dev Cell
; 29(1): 7-19, 2014 Apr 14.
Article
en En
| MEDLINE
| ID: mdl-24735877
ABSTRACT
Telomere length homeostasis is essential for genomic stability and unlimited self-renewal of embryonic stem cells (ESCs). We show that telomere-associated protein Rif1 is required to maintain telomere length homeostasis by negatively regulating Zscan4 expression, a critical factor for telomere elongation by recombination. Depletion of Rif1 results in terminal hyperrecombination, telomere length heterogeneity, and chromosomal fusions. Reduction of Zscan4 by shRNA significantly rescues telomere recombination defects of Rif1-depleted ESCs and associated embryonic lethality. Further, Rif1 negatively modulates Zscan4 expression by maintaining H3K9me3 levels at subtelomeric regions. Mechanistically, Rif1 interacts and stabilizes H3K9 methylation complex. Thus, Rif1 regulates telomere length homeostasis of ESCs by mediating heterochromatic silencing.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Heterocromatina
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Silenciador del Gen
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Proteínas de Unión a Telómeros
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Células Madre Embrionarias
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Homeostasis del Telómero
Límite:
Animals
Idioma:
En
Revista:
Dev Cell
Asunto de la revista:
EMBRIOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
China