Reprogramming of Polycomb-Mediated Gene Silencing in Embryonic Stem Cells by the miR-290 Family and the Methyltransferase Ash1l.
Stem Cell Reports
; 5(6): 971-978, 2015 Dec 08.
Article
em En
| MEDLINE
| ID: mdl-26549848
ABSTRACT
Members of the miR-290 family are the most abundantly expressed microRNAs (miRNAs) in mouse embryonic stem cells (ESCs). They regulate aspects of differentiation, pluripotency, and proliferation of ESCs, but the molecular program that they control has not been fully delineated. In the absence of Dicer, ESCs fail to express mature miR-290 miRNAs and have selective aberrant overexpression of Hoxa, Hoxb, Hoxc, and Hoxd genes essential for body plan patterning during embryogenesis, but they do not undergo a full differentiation program. Introduction of mature miR-291 into DCR(-/-) ESCs restores Hox gene silencing. This was attributed to the unexpected regulation of Polycomb-mediated gene targeting by miR-291. We identified the methyltransferase Ash1l as a pivotal target of miR-291 mediating this effect. Collectively, our data shed light on the role of Dicer in ESC homeostasis by revealing a facet of molecular regulation by the miR-290 family.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Histona-Lisina N-Metiltransferase
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MicroRNAs
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Células-Tronco Embrionárias
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Reprogramação Celular
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Proteínas do Grupo Polycomb
Limite:
Animals
Idioma:
En
Revista:
Stem Cell Reports
Ano de publicação:
2015
Tipo de documento:
Article