MicroRNAs of the miR-290-295 Family Maintain Bivalency in Mouse Embryonic Stem Cells

Research output: Contribution to journalJournal articleResearchpeer-review

Bryony Graham, Antoine Marcais, Gopuraja Dharmalingam, Thomas Carroll, Chryssa Kanellopoulou, Johannes Graumann, Tatyana B Nesterova, Anna Bermange, Pijus Brazauskas, Barbara Xella, Skirmantas Kriaucionis, Douglas R Higgs, Neil Brockdorff, Matthias Mann, Amanda G Fisher, Matthias Merkenschlager

Numerous developmentally regulated genes in mouse embryonic stem cells (ESCs) are marked by both active (H3K4me3)- and polycomb group (PcG)-mediated repressive (H3K27me3) histone modifications. This bivalent state is thought to be important for transcriptional poising, but the mechanisms that regulate bivalent genes and the bivalent state remain incompletely understood. Examining the contribution of microRNAs (miRNAs) to the regulation of bivalent genes, we found that the miRNA biogenesis enzyme DICER was required for the binding of the PRC2 core components EZH2 and SUZ12, and for the presence of the PRC2-mediated histone modification H3K27me3 at many bivalent genes. Genes that lost bivalency were preferentially upregulated at the mRNA and protein levels. Finally, reconstituting Dicer-deficient ESCs with ESC miRNAs restored bivalent gene repression and PRC2 binding at formerly bivalent genes. Therefore, miRNAs regulate bivalent genes and the bivalent state itself.

Original languageEnglish
JournalStem Cell Reports
Issue number5
Pages (from-to)635-642
Number of pages8
Publication statusPublished - 10 May 2016
Externally publishedYes

    Research areas

  • Animals, Cell Differentiation, DEAD-box RNA Helicases, Enhancer of Zeste Homolog 2 Protein, Gene Expression Regulation, Developmental, Histone Code, Histone-Lysine N-Methyltransferase, Mice, MicroRNAs, Mouse Embryonic Stem Cells, Polycomb Repressive Complex 2, Promoter Regions, Genetic, Ribonuclease III, Transcriptional Activation, Journal Article

ID: 186876844