POLYCOMB-MEDIATED SILENCING OF MIR-8 IS REQUIRED FOR MAINTENANCE OF INTESTINAL STEMNESS IN DROSOPHILA MELANOGASTER

Polycomb-mediated silencing of miR-8 is required for maintenance of intestinal stemness in Drosophila melanogaster

Polycomb-mediated silencing of miR-8 is required for maintenance of intestinal stemness in Drosophila melanogaster

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Abstract Balancing maintenance of self-renewal and differentiation is a key property of adult stem cells.The epigenetic mechanisms controlling this balance remain largely unknown.Herein, we report that the Polycomb Repressive Complex 2 (PRC2) is required for maintenance of the intestinal stem cell (ISC) pool in the adult female Drosophila melanogaster.We show that Chafer Accessories loss of PRC2 activity in ISCs by RNAi-mediated knockdown or genetic ablation of the enzymatic subunit Enhancer of zeste, E(z), results in 5 Piece Full Poster Bedroom loss of stemness and precocious differentiation of enteroblasts to enterocytes.Mechanistically, we have identified the microRNA miR-8 as a critical target of E(z)/PRC2-mediated tri-methylation of histone H3 at Lys27 (H3K27me3) and uncovered a dynamic relationship between E(z), miR-8 and Notch signaling in controlling stemness versus differentiation of ISCs.

Collectively, these findings uncover a hitherto unrecognized epigenetic layer in the regulation of stem cell specification that safeguards intestinal homeostasis.

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