Epigenetic regulation of survivin by Bmi1 is cell type specific during corticogenesis and in gliomas.
Stem Cells
; 31(1): 190-202, 2013 Jan.
Article
en En
| MEDLINE
| ID: mdl-23132836
Polycomb group proteins are essential regulators of stem cell function during embryonic development and in adult tissue homeostasis. Bmi1, a key component of the Polycomb Repressive Complex 1, is highly expressed in undifferentiated neural stem cells (NSC) as well as in several human cancers including high-grade gliomas--highly aggressive brain tumors. Using a conditional gene activation approach in mice, we show that overexpression of Bmi1 induces repressive epigenetic regulation of the promoter of Survivin, a well-characterized antiapoptotic protein. This phenomenon is cell type-specific and it leads to apoptotic death of progenitor cells exclusively upon commitment toward a neuronal fate. Moreover, we show that this is triggered by increased oxidative stress-induced DNA damage. In contrast, undifferentiated NSC as well as glioma-initiating cells display an open chromatin configuration at the Survivin promoter and do not undergo apoptotic death. These findings raise the possibility that normal and neoplastic stem cells depend on the same mechanism for surviving the hyperproliferative state induced by increased Bmi1 expression.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Proteínas Proto-Oncogénicas
/
Proteínas Inhibidoras de la Apoptosis
/
Células-Madre Neurales
/
Complejo Represivo Polycomb 1
/
Glioma
Límite:
Animals
Idioma:
En
Revista:
Stem Cells
Año:
2013
Tipo del documento:
Article
País de afiliación:
Reino Unido
Pais de publicación:
Reino Unido