Abstract
PRC2 (Polycomb repressive complex 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 (embryonic ectoderm development) 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.
Highlights
PRC2 is involved in many biological processes, yet how the function of PRC2 is regulated is largely unknown
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
It has been shown that PRC2 is involved in various biological processes and is especially important for the regulation of stem cell pluripotency and differentiation [33]
Summary
PRC2 is involved in many biological processes, yet how the function of PRC2 is regulated is largely unknown. Binding of miR-323-3p to Eed mRNA results in reduced EED protein abundance and cellular H3K27me levels in mouse and human cells. Binding of miR-323-3p to Eed mRNA resulted in reduced EED protein abundance and cellular H3K27me levels, indicating decreased PRC2 activity Such regulation seems to be conserved among mammals, at least between mice and humans. Mouse embryonic fibroblast cells had much higher miR-323-3p expression and nearly undetectable H3K27me levels These findings identify miR-323-3p as a new regulator for PRC2 and provide a new approach for regulating PRC2 activity via microRNAs. Polycomb group proteins are key epigenetic regulators for genes involved in development and cell fate specification [1,2,3,4]. The pairing between miR-323-3p and Eed mRNA interrupted the methyltransferase activity of PRC2 and resulted in reduced H3K27me levels in high miR-323-3p-expressing cells
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