title: Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome.
abstract: The Polycomb repressive complexes PRC1 and PRC2 maintain embryonic stem cell (ESC) pluripotency by silencing lineage-specifying developmental regulator genes. Emerging evidence suggests that Polycomb complexes act through controlling spatial genome organization. We show that PRC1 functions as a master regulator of mouse ESC genome architecture by organizing genes in three-dimensional interaction networks. The strongest spatial network is composed of the four Hox gene clusters and early developmental transcription factor genes, the majority of which contact poised enhancers. Removal of Polycomb repression leads to disruption of promoter-promoter contacts in the Hox gene network. In contrast, promoter-enhancer contacts are maintained in the absence of Polycomb repression, with accompanying widespread acquisition of active chromatin signatures at network enhancers and pronounced transcriptional upregulation of network genes. Thus, PRC1 physically constrains developmental transcription factor genes and their enhancers in a silenced but poised spatial network. We propose that the selective release of genes from this spatial network underlies cell fate specification during early embryonic development.
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors: Stefan
authors: S
authors: Schoenfelder
authors: EMBL European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors: Robert
authors: R
authors: Sugar
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors: Andrew
authors: A
authors: Dimond
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors: Biola-Maria
authors: BM
authors: Javierre
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors: Harry
authors: H
authors: Armstrong
authors: Cancer Research UK London Research Institute, London, UK.|Department of Genetics, Evolution & Environment, University College London, London, UK.
authors: Borbala
authors: B
authors: Mifsud
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.|Department of Biochemistry, Oxford University, Oxford, UK.
authors: Emilia
authors: E
authors: Dimitrova
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors: Louise
authors: L
authors: Matheson
authors: Cancer Research UK London Research Institute, London, UK.|present address: Okinawa Institute for Science and Technology Graduate University, Okinawa, Japan.
authors: Filipe
authors: F
authors: Tavares-Cadete
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors: Mayra
authors: M
authors: Furlan-Magaril
authors: Bioinformatics, The Babraham Institute, Cambridge, UK.
authors: Anne
authors: A
authors: Segonds-Pichon
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors: Wiktor
authors: W
authors: Jurkowski
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.|Bioinformatics, The Babraham Institute, Cambridge, UK.
authors: Steven W
authors: SW
authors: Wingett
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors: Kristina
authors: K
authors: Tabbada
authors: Bioinformatics, The Babraham Institute, Cambridge, UK.
authors: Simon
authors: S
authors: Andrews
authors: Agilent Technologies Inc., Santa Clara, California, USA.
authors: Bram
authors: B
authors: Herman
authors: Agilent Technologies Inc., Santa Clara, California, USA.
authors: Emily
authors: E
authors: LeProust
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors: Cameron S
authors: CS
authors: Osborne
authors: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors: Haruhiko
authors: H
authors: Koseki
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors: Peter
authors: P
authors: Fraser
authors: EMBL European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.|Cancer Research UK London Research Institute, London, UK.|Department of Genetics, Evolution & Environment, University College London, London, UK.|Okinawa Institute for Science and Technology Graduate University, Okinawa, Japan.
authors: Nicholas M
authors: NM
authors: Luscombe
authors: Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
authors: Sarah
authors: S
authors: Elderkin
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000378:metabolism*; D016678:Genome; D051379:Mice; D063146:Polycomb-Group Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic
chemical_list: D063146:Polycomb-Group Proteins