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MicroRNA-323-3p Regulates the Activity of Polycomb Repressive Complex 2 (PRC2) via Targeting the mRNA of Embryonic Ectoderm Development ( Eed ) Gene in Mouse Embryonic Stem Cells *

Journal of Biological Chemistry, ISSN: 0021-9258, Vol: 288, Issue: 33, Page: 23659-23665
2013
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Article Description

PRC2 ( P olycomb r epressive c omplex 2 ) mediates epigenetic gene silencing by catalyzing the triple methylation of histone H3 Lys-27 (H3K27me3) to establish a repressive epigenetic state. PRC2 is involved in the regulation of many fundamental biological processes and is especially essential for embryonic stem cells. However, how the formation and function of PRC2 are regulated is largely unknown. Here, we show that a microRNA encoded by the imprinted Dlk1-Dio3 region of mouse chromosome 12, miR-323-3p, targets Eed ( e mbryonic e ctoderm d evelopment) mRNA, which encodes one of the core components of PRC2, the EED protein. Binding of miR-323-3p to Eed mRNA resulted in reduced EED protein abundance and cellular H3K27me3 levels, indicating decreased PRC2 activity. Such regulation seems to be conserved among mammals, at least between mice and humans. We demonstrate that induced pluripotent stem cells with varied developmental abilities had different miR-323-3p as well as EED and H3K27me3 levels, indicating that miR-323-3p may be involved in the regulation of stem cell pluripotency through affecting PRC2 activity. Mouse embryonic fibroblast cells had much higher miR-323-3p expression and nearly undetectable H3K27me3 levels. These findings identify miR-323-3p as a new regulator for PRC2 and provide a new approach for regulating PRC2 activity via microRNAs. Background: PRC2 is involved in many biological processes, yet how the function of PRC2 is regulated is largely unknown. Results: The 3′-UTR of Eed mRNA contains miR-323-3p-binding sites. Binding of miR-323-3p to Eed mRNA results in reduced EED protein abundance and cellular H3K27me3 levels in mouse and human cells. Conclusion: miR-323-3p regulates PRC2 activity via targeting Eed. Significance: The work identifies miR-323-3p as a new regulator of PRC2.

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