Poster Sessions

Dev-30

Aster Juan

A. Juan, R. Kumar, J. Marx, R. Young, V. Sartorelli

Post-Transcriptional Regulation of the Polycomb Ezh2 by microRNA-214 In Skeletal Muscle and Embryonic Stem Cells

The Polycomb group (PcG) proteins are recruited to genes encoding developmental regulators and prevent their transcription, thus maintaining pluripotency of embryonic stem (ES) cells. PcG proteins also regulate differentiation of committed cell lineages, including that of skeletal muscle cells (SMC). In this study, we have addressed the question of how PcG-mediated transcriptional repression is overcome to allow differentiation of SMC and ES cells. Our findings reveal that PcG proteins occupy an intronic region containing the microRNA miR-214, when this region is repressed in undifferentiated SMC. Cell differentiation coincides with disengagement of PcG proteins and activation of miR-214 transcription. miR-214 targets the 3’UTR of the PcG Ezh2 mRNA, leading to reduced Ezh2 protein accumulation. Decreased Ezh2 anticipates SMC differentiation, and initiates unscheduled transcription of developmental regulators in ES cells. Thus, PcG-dependent gene repression is resolved by both transcriptional and miR-214-mediated post-transcriptional regulation of Ezh2.