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

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

doi:10.1016/j.stemcr.2016.03.005

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

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

15 Citations (Scopus)

Abstract

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 language	English
Journal	Stem Cell Reports
Volume	6
Issue number	5
Pages (from-to)	635-642
Number of pages	8
ISSN	2213-6711
DOIs	https://doi.org/10.1016/j.stemcr.2016.03.005
Publication status	Published - 10 May 2016
Externally published	Yes

Keywords

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

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Graham, B., Marcais, A., Dharmalingam, G., Carroll, T., Kanellopoulou, C., Graumann, J., Nesterova, T. B., Bermange, A., Brazauskas, P., Xella, B., Kriaucionis, S., Higgs, D. R., Brockdorff, N., Mann, M., Fisher, A. G., & Merkenschlager, M. (2016). MicroRNAs of the miR-290-295 Family Maintain Bivalency in Mouse Embryonic Stem Cells. Stem Cell Reports, 6(5), 635-642. https://doi.org/10.1016/j.stemcr.2016.03.005

Graham, B, Marcais, A, Dharmalingam, G, Carroll, T, Kanellopoulou, C, Graumann, J, Nesterova, TB, Bermange, A, Brazauskas, P, Xella, B, Kriaucionis, S, Higgs, DR, Brockdorff, N, Mann, M, Fisher, AG & Merkenschlager, M 2016, 'MicroRNAs of the miR-290-295 Family Maintain Bivalency in Mouse Embryonic Stem Cells', Stem Cell Reports, vol. 6, no. 5, pp. 635-642. https://doi.org/10.1016/j.stemcr.2016.03.005

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title = "MicroRNAs of the miR-290-295 Family Maintain Bivalency in Mouse Embryonic Stem Cells",

abstract = "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.",

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

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T1 - MicroRNAs of the miR-290-295 Family Maintain Bivalency in Mouse Embryonic Stem Cells

AU - Graham, Bryony

AU - Marcais, Antoine

AU - Dharmalingam, Gopuraja

AU - Carroll, Thomas

AU - Kanellopoulou, Chryssa

AU - Graumann, Johannes

AU - Nesterova, Tatyana B

AU - Bermange, Anna

AU - Brazauskas, Pijus

AU - Xella, Barbara

AU - Kriaucionis, Skirmantas

AU - Higgs, Douglas R

AU - Brockdorff, Neil

AU - Mann, Matthias

AU - Fisher, Amanda G

AU - Merkenschlager, Matthias

PY - 2016/5/10

Y1 - 2016/5/10

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Differentiation

KW - DEAD-box RNA Helicases

KW - Enhancer of Zeste Homolog 2 Protein

KW - Gene Expression Regulation, Developmental

KW - Histone Code

KW - Histone-Lysine N-Methyltransferase

KW - Mice

KW - MicroRNAs

KW - Mouse Embryonic Stem Cells

KW - Polycomb Repressive Complex 2

KW - Promoter Regions, Genetic

KW - Ribonuclease III

KW - Transcriptional Activation

KW - Journal Article

U2 - 10.1016/j.stemcr.2016.03.005

DO - 10.1016/j.stemcr.2016.03.005

M3 - Journal article

C2 - 27150236

SN - 2213-6711

VL - 6

SP - 635

EP - 642

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 5

ER -

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

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Keywords

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