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Network analysis of promoter interactions reveals the hierarchical differences in genome organisation between human pluripotent states

View ORCID ProfilePeter Chovanec, View ORCID ProfileAmanda J. Collier, View ORCID ProfileChristel Krueger, Csilla Várnai, Stefan Schoenfelder, View ORCID ProfileAnne Corcoran, View ORCID ProfilePeter J. Rugg-Gunn
doi: https://doi.org/10.1101/2019.12.13.875286
Peter Chovanec
1Lymphocyte Signalling Programme, Babraham Institute, Cambridge, CB22 3AT, U.K.
2Nuclear Dynamics Programme, Babraham Institute, Cambridge, CB22 3AT, U.K.
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  • ORCID record for Peter Chovanec
Amanda J. Collier
3Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, U.K.
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  • ORCID record for Amanda J. Collier
Christel Krueger
3Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, U.K.
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  • ORCID record for Christel Krueger
Csilla Várnai
2Nuclear Dynamics Programme, Babraham Institute, Cambridge, CB22 3AT, U.K.
4Centre for Computational Biology, University of Birmingham, B15 2TT Birmingham, U.K.
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Stefan Schoenfelder
2Nuclear Dynamics Programme, Babraham Institute, Cambridge, CB22 3AT, U.K.
3Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, U.K.
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Anne Corcoran
1Lymphocyte Signalling Programme, Babraham Institute, Cambridge, CB22 3AT, U.K.
2Nuclear Dynamics Programme, Babraham Institute, Cambridge, CB22 3AT, U.K.
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Peter J. Rugg-Gunn
3Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, U.K.
5Wellcome – MRC Cambridge Stem Cell Institute, Cambridge CB2 1QR, U.K.
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  • For correspondence: peter.rugg-gunn@babraham.ac.uk
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SUMMARY

A complex and poorly understood interplay between 3D genome organisation, transcription factors and chromatin state underpins cell identity. To gain a systems-level understanding of this interplay, we generated a high-resolution atlas of annotated chromatin interactions in naïve and primed human pluripotent stem cells and developed a network-graph approach to examine the atlas at multiple spatial scales. Investigating chromatin interactions as a network uncovered highly connected hubs that changed substantially in interaction frequency and in transcriptional co-regulation between pluripotent states. Small hubs frequently merged to form larger networks in primed cells, often linked by newly-formed Polycomb-associated interactions. Importantly, we identified state-specific differences in enhancer activity and interactivity that corresponded with widespread reconfiguration of transcription factor binding and target gene expression. These findings provide multilayered insights into the gene regulatory control of human pluripotency and our systems-based network approach could be applied broadly to uncover new principles of 3D genome organisation.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 13, 2019.
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Network analysis of promoter interactions reveals the hierarchical differences in genome organisation between human pluripotent states
Peter Chovanec, Amanda J. Collier, Christel Krueger, Csilla Várnai, Stefan Schoenfelder, Anne Corcoran, Peter J. Rugg-Gunn
bioRxiv 2019.12.13.875286; doi: https://doi.org/10.1101/2019.12.13.875286
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Network analysis of promoter interactions reveals the hierarchical differences in genome organisation between human pluripotent states
Peter Chovanec, Amanda J. Collier, Christel Krueger, Csilla Várnai, Stefan Schoenfelder, Anne Corcoran, Peter J. Rugg-Gunn
bioRxiv 2019.12.13.875286; doi: https://doi.org/10.1101/2019.12.13.875286

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