The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements
Por:
Schoenfelder S., Furlan-Magaril M., Mifsud B., Tavares-Cadete F., Sugar R., Javierre B.-M., Nagano T., Katsman Y., Sakthidevi M., Wingett S.W., Dimitrova E., Dimond A., Edelman L.B., Elderkin S., Tabbada K., Darbo E., Andrews S., Herman B., Higgs A., LeProust E., Osborne C.S., Mitchell J.A., Luscombe N.M., Fraser P.
Publicada:
1 ene 2015
Resumen:
The mammalian genome harbors up to one million regulatory elements often located at great distances from their target genes. Long-range elements control genes through physical contact with promoters and can be recognized by the presence of specific histone modifications and transcription factor binding. Linking regulatory elements to specific promoters genome-wide is currently impeded by the limited resolution of high-throughput chromatin interaction assays. Here we apply a sequence capture approach to enrich Hi-C libraries for >22,000 annotated mouse promoters to identify statistically significant, long-range interactions at restriction fragment resolution, assigning long-range interacting elements to their target genes genome-wide in embryonic stem cells and fetal liver cells. The distal sites contacting active genes are enriched in active histone modifications and transcription factor occupancy, whereas inactive genes contact distal sites with repressive histone marks, demonstrating the regulatory potential of the distal elements identified. Furthermore, we find that coregulated genes cluster nonrandomly in spatial interaction networks correlated with their biological function and expression level. Interestingly, we find the strongest gene clustering in ES cells between transcription factor genes that control key developmental processes in embryogenesis. The results provide the first genome-wide catalog linking gene promoters to their longrange interacting elements and highlight the complex spatial regulatory circuitry controlling mammalian gene expression. © 2015 Schoenfelder et al.
Filiaciones:
Schoenfelder S.:
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
Furlan-Magaril M.:
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
Mifsud B.:
University College London, UCL Genetics Institute, Department of Genetics, Evolution and Environment, London, United Kingdom
Cancer Research UK, London Research Institute, London, United Kingdom
Tavares-Cadete F.:
University College London, UCL Genetics Institute, Department of Genetics, Evolution and Environment, London, United Kingdom
Cancer Research UK, London Research Institute, London, United Kingdom
Sugar R.:
Cancer Research UK, London Research Institute, London, United Kingdom
EMBL European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom
Javierre B.-M.:
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
Nagano T.:
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
Katsman Y.:
Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada
Sakthidevi M.:
Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada
Wingett S.W.:
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
Bioinformatics Group, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
Dimitrova E.:
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
Dimond A.:
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
Edelman L.B.:
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
Elderkin S.:
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
Tabbada K.:
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
Darbo E.:
University College London, UCL Genetics Institute, Department of Genetics, Evolution and Environment, London, United Kingdom
Cancer Research UK, London Research Institute, London, United Kingdom
Andrews S.:
Bioinformatics Group, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
Herman B.:
Agilent Technologies, Inc., Santa Clara, CA, United States
Higgs A.:
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, Babraham Research Campus, Cambridge, United Kingdom
Mitchell J.A.:
Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada
Luscombe N.M.:
University College London, UCL Genetics Institute, Department of Genetics, Evolution and Environment, London, United Kingdom
Cancer Research UK, London Research Institute, London, United Kingdom
Okinawa Institute for Science and Technology, Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa, Japan
Fraser P.:
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
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