Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome
Por:
Schoenfelder S., Sugar R., Dimond A., Javierre B.-M., Armstrong H., Mifsud B., Dimitrova E., Matheson L., Tavares-Cadete F., Furlan-Magaril M., Segonds-Pichon A., Jurkowski W., Wingett S.W., Tabbada K., Andrews S., Herman B., Leproust E., Osborne C.S., Koseki H., Fraser P., Luscombe N.M., Elderkin S.
Publicada:
1 ene 2015
Categoría:
Genetics
Resumen:
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. © 2015 Nature America, Inc.
Filiaciones:
Schoenfelder S.:
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom
Sugar R.:
European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
Dimond A.:
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom
Javierre B.-M.:
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom
Armstrong H.:
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom
Mifsud B.:
Cancer Research UK London Research Institute, London, United Kingdom
Department of Genetics,Evolution and Environment, University College London, London, United Kingdom
Dimitrova E.:
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom
Department of Biochemistry, Oxford University, Oxford, United Kingdom
Matheson L.:
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom
Tavares-Cadete F.:
Cancer Research UK London Research Institute, London, United Kingdom
Okinawa Institute for Science and Technology Graduate University, Okinawa, Japan
Furlan-Magaril M.:
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom
Segonds-Pichon A.:
Bioinformatics Group, Babraham Institute, Cambridge, United Kingdom
Jurkowski W.:
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom
Wingett S.W.:
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom
Bioinformatics Group, Babraham Institute, Cambridge, United Kingdom
Tabbada K.:
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom
Andrews S.:
Bioinformatics Group, Babraham Institute, Cambridge, United Kingdom
Herman B.:
Agilent Technologies Inc., Santa Clara, CA, United States
Leproust E.:
Agilent Technologies Inc., Santa Clara, CA, United States
Osborne C.S.:
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom
Koseki H.:
Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Fraser P.:
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom
Luscombe N.M.:
European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
Cancer Research UK London Research Institute, London, United Kingdom
Department of Genetics,Evolution and Environment, University College London, London, United Kingdom
Okinawa Institute for Science and Technology, Graduate University, Okinawa, Japan
Elderkin S.:
Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom
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