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Reprogramming of Polycomb-Mediated Gene Silencing in Embryonic Stem Cells by the miR-290 Family and the Methyltransferase Ash1l.

Authors :
Kanellopoulou C
Gilpatrick T
Kilaru G
Burr P
Nguyen CK
Morawski A
Lenardo MJ
Muljo SA
Source :
Stem cell reports [Stem Cell Reports] 2015 Dec 08; Vol. 5 (6), pp. 971-978. Date of Electronic Publication: 2015 Nov 05.
Publication Year :
2015

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.<br /> (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
2213-6711
Volume :
5
Issue :
6
Database :
MEDLINE
Journal :
Stem cell reports
Publication Type :
Academic Journal
Accession number :
26549848
Full Text :
https://doi.org/10.1016/j.stemcr.2015.10.001