EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells

Malte Beringer; Paola Pisano; Valerio Di Carlo; Enrique Blanco; Paul Chammas; Pedro Vizán; Arantxa Gutiérrez; Sergi Aranda; Bernhard Payer; Michael Wierer; Luciano Di Croce

doi:10.1016/j.molcel.2016.10.018

EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells

Malte Beringer, Paola Pisano, Valerio Di Carlo, Enrique Blanco, Paul Chammas, Pedro Vizán, Arantxa Gutiérrez, Sergi Aranda, Bernhard Payer, Michael Wierer, Luciano Di Croce

Research output: Indexed journal article › Article › peer-review

106 Citations (Scopus)

Abstract

The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these levels remain unknown. Here, we describe Elongin BC as a binding factor at the promoters of bivalent sites. Biochemical and genome-wide analyses show that Elongin BC is associated with Polycomb Repressive Complex 2 (PRC2) in pluripotent stem cells. Elongin BC is recruited to chromatin by the PRC2-associated factor EPOP (Elongin BC and Polycomb Repressive Complex 2 Associated Protein, also termed C17orf96, esPRC2p48, E130012A19Rik), a protein expressed in the inner cell mass of the mouse blastocyst. Both EPOP and Elongin BC are required to maintain low levels of expression at PRC2 genomic targets. Our results indicate that keeping the balance between activating and repressive cues is a more general feature of chromatin in pluripotent stem cells than previously appreciated.

Original language	English
Pages (from-to)	645-658
Number of pages	14
Journal	Molecular Cell
Volume	64
Issue number	4
DOIs	https://doi.org/10.1016/j.molcel.2016.10.018
Publication status	Published - 17 Nov 2016
Externally published	Yes

Keywords

Elongin
Polycomb
chromatin
epigenetics
gene regulation
pre-implantation development
stem cells
transcription

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10.1016/j.molcel.2016.10.018

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title = "EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells",

abstract = "The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these levels remain unknown. Here, we describe Elongin BC as a binding factor at the promoters of bivalent sites. Biochemical and genome-wide analyses show that Elongin BC is associated with Polycomb Repressive Complex 2 (PRC2) in pluripotent stem cells. Elongin BC is recruited to chromatin by the PRC2-associated factor EPOP (Elongin BC and Polycomb Repressive Complex 2 Associated Protein, also termed C17orf96, esPRC2p48, E130012A19Rik), a protein expressed in the inner cell mass of the mouse blastocyst. Both EPOP and Elongin BC are required to maintain low levels of expression at PRC2 genomic targets. Our results indicate that keeping the balance between activating and repressive cues is a more general feature of chromatin in pluripotent stem cells than previously appreciated.",

keywords = "Elongin, Polycomb, chromatin, epigenetics, gene regulation, pre-implantation development, stem cells, transcription",

author = "Malte Beringer and Paola Pisano and {Di Carlo}, Valerio and Enrique Blanco and Paul Chammas and Pedro Viz{\'a}n and Arantxa Guti{\'e}rrez and Sergi Aranda and Bernhard Payer and Michael Wierer and {Di Croce}, Luciano",

note = "Funding Information: We thank R. Liefke and Y. Shi for data sharing and for EPOP(L40A) plasmid. We thank the CRG Genomics, Proteomics, and Advanced Light Microscopy Units. We also thank all members of L.D.C.{\textquoteright}s laboratory for discussion and S. Ojanguren and V. Raker for help in preparation of the figures and text editing, respectively. We acknowledge support of the Spanish Ministry of Economy and Competitiveness ( SAF2013-48926-P ), Centro de Excelencia Severo Ochoa 2013-2017 ( SEV-2012-0208 ), and a Plan Estatal Grant to B.P. ( BFU2014-55275-P ). This work was supported by grants from AGAUR , Fundaci{\'o} “La Marat{\'o} de TV3,” the Fundaci{\'o}n Vencer El C{\'a}ncer (VEC) , and the EU FP7 Programs 4DCellFate ( 277899 ), as well as Marie Curie Actions ( FP7/2007-2013: 608959 ). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

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AU - Beringer, Malte

AU - Pisano, Paola

AU - Di Carlo, Valerio

AU - Blanco, Enrique

AU - Chammas, Paul

AU - Vizán, Pedro

AU - Gutiérrez, Arantxa

AU - Aranda, Sergi

AU - Payer, Bernhard

AU - Wierer, Michael

AU - Di Croce, Luciano

N1 - Funding Information: We thank R. Liefke and Y. Shi for data sharing and for EPOP(L40A) plasmid. We thank the CRG Genomics, Proteomics, and Advanced Light Microscopy Units. We also thank all members of L.D.C.’s laboratory for discussion and S. Ojanguren and V. Raker for help in preparation of the figures and text editing, respectively. We acknowledge support of the Spanish Ministry of Economy and Competitiveness ( SAF2013-48926-P ), Centro de Excelencia Severo Ochoa 2013-2017 ( SEV-2012-0208 ), and a Plan Estatal Grant to B.P. ( BFU2014-55275-P ). This work was supported by grants from AGAUR , Fundació “La Marató de TV3,” the Fundación Vencer El Cáncer (VEC) , and the EU FP7 Programs 4DCellFate ( 277899 ), as well as Marie Curie Actions ( FP7/2007-2013: 608959 ). Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/11/17

Y1 - 2016/11/17

N2 - The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these levels remain unknown. Here, we describe Elongin BC as a binding factor at the promoters of bivalent sites. Biochemical and genome-wide analyses show that Elongin BC is associated with Polycomb Repressive Complex 2 (PRC2) in pluripotent stem cells. Elongin BC is recruited to chromatin by the PRC2-associated factor EPOP (Elongin BC and Polycomb Repressive Complex 2 Associated Protein, also termed C17orf96, esPRC2p48, E130012A19Rik), a protein expressed in the inner cell mass of the mouse blastocyst. Both EPOP and Elongin BC are required to maintain low levels of expression at PRC2 genomic targets. Our results indicate that keeping the balance between activating and repressive cues is a more general feature of chromatin in pluripotent stem cells than previously appreciated.

AB - The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these levels remain unknown. Here, we describe Elongin BC as a binding factor at the promoters of bivalent sites. Biochemical and genome-wide analyses show that Elongin BC is associated with Polycomb Repressive Complex 2 (PRC2) in pluripotent stem cells. Elongin BC is recruited to chromatin by the PRC2-associated factor EPOP (Elongin BC and Polycomb Repressive Complex 2 Associated Protein, also termed C17orf96, esPRC2p48, E130012A19Rik), a protein expressed in the inner cell mass of the mouse blastocyst. Both EPOP and Elongin BC are required to maintain low levels of expression at PRC2 genomic targets. Our results indicate that keeping the balance between activating and repressive cues is a more general feature of chromatin in pluripotent stem cells than previously appreciated.

KW - Elongin

KW - Polycomb

KW - chromatin

KW - epigenetics

KW - gene regulation

KW - pre-implantation development

KW - stem cells

KW - transcription

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DO - 10.1016/j.molcel.2016.10.018

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SN - 1097-2765

VL - 64

SP - 645

EP - 658

JO - Molecular Cell

JF - Molecular Cell

IS - 4

ER -

EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells

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Keywords

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