1. Stem Cells and Regenerative Medicine
  2. Chromosomes and Gene Expression

Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells

  1. Paula Freire-Pritchett
  2. Stefan Schoenfelder
  3. Csilla Várnai
  4. Steven W Wingett
  5. Jonathan Cairns
  6. Amanda J Collier
  7. Raquel García-Vílchez
  8. Mayra Furlan-Magaril
  9. Cameron S Osborne
  10. Peter J Fraser
  11. Peter J Rugg-Gunn  Is a corresponding author
  12. Mikhail Spivakov  Is a corresponding author
  1. The Babraham Institute, United Kingdom
  2. Universidad Nacional Autónoma de México, Mexico
  3. King's College London School of Medicine, United Kingdom
https://doi.org/10.7554/eLife.21926
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  1. Paula Freire-Pritchett
  2. Stefan Schoenfelder
  3. Csilla Várnai
  4. Steven W Wingett
  5. Jonathan Cairns
  6. Amanda J Collier
  7. Raquel García-Vílchez
  8. Mayra Furlan-Magaril
  9. Cameron S Osborne
  10. Peter J Fraser
  11. Peter J Rugg-Gunn
  12. Mikhail Spivakov
(2017)
Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells
eLife 6:e21926.
https://doi.org/10.7554/eLife.21926
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  3. Download .RIS

Abstract

Long-range cis-regulatory elements such as enhancers coordinate cell-specific transcriptional programmes by engaging in DNA looping interactions with target promoters. Deciphering the interplay between the promoter connectivity and activity of cis-regulatory elements during lineage commitment is crucial for understanding developmental transcriptional control. Here, we use Promoter Capture Hi-C to generate a high-resolution atlas of chromosomal interactions involving ~22,000 gene promoters in human pluripotent and lineage-committed cells, identifying putative target genes for known and predicted enhancer elements. We reveal extensive dynamics of cis-regulatory contacts upon lineage commitment, including the acquisition and loss of promoter interactions. This spatial rewiring occurs preferentially with predicted changes in the activity of cis-regulatory elements, and is associated with changes in target gene expression. Our results provide a global and integrated view of promoter interactome dynamics during lineage commitment of human pluripotent cells.

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Article and author information

Author details

  1. Paula Freire-Pritchett

    Nuclear Dynamics Programme, The Babraham Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  2. Stefan Schoenfelder

    Nuclear Dynamics Programme, The Babraham Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  3. Csilla Várnai

    Nuclear Dynamics Programme, The Babraham Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  4. Steven W Wingett

    Nuclear Dynamics Programme, The Babraham Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  5. Jonathan Cairns

    Nuclear Dynamics Programme, The Babraham Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  6. Amanda J Collier

    Epigenetics Programme, The Babraham Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  7. Raquel García-Vílchez

    Epigenetics Programme, The Babraham Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  8. Mayra Furlan-Magaril

    Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
    Competing interests
    The authors declare that no competing interests exist.

  9. Cameron S Osborne

    Department of Genetics and Molecular Medicine, King's College London School of Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  10. Peter J Fraser

    Nuclear Dynamics Programme, The Babraham Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  11. Peter J Rugg-Gunn

    Epigenetics Programme, The Babraham Institute, Cambridge, United Kingdom
    For correspondence
    peter.rugg-gunn@babraham.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

  12. Mikhail Spivakov

    Nuclear Dynamics Programme, The Babraham Institute, Cambridge, United Kingdom
    For correspondence
    mikhail.spivakov@babraham.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0383-3943

Funding

Wellcome (WT093736)

  • Peter J Rugg-Gunn

Biotechnology and Biological Sciences Research Council (BB/J004480/1)

  • Paula Freire-Pritchett
  • Stefan Schoenfelder
  • Csilla Várnai
  • Steven W Wingett
  • Jonathan Cairns
  • Mayra Furlan-Magaril
  • Peter J Fraser
  • Mikhail Spivakov

Medical Research Council (MR/J003808/1)

  • Amanda J Collier

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Job Dekker, University of Massachusetts Medical School, United States

Version history

  1. Received: September 28, 2016
  2. Accepted: March 22, 2017
  3. Accepted Manuscript published: March 23, 2017 (version 1)
  4. Version of Record published: April 27, 2017 (version 2)

Copyright

© 2017, Freire-Pritchett et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Paula Freire-Pritchett
  2. Stefan Schoenfelder
  3. Csilla Várnai
  4. Steven W Wingett
  5. Jonathan Cairns
  6. Amanda J Collier
  7. Raquel García-Vílchez
  8. Mayra Furlan-Magaril
  9. Cameron S Osborne
  10. Peter J Fraser
  11. Peter J Rugg-Gunn
  12. Mikhail Spivakov
(2017)
Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells
eLife 6:e21926.
https://doi.org/10.7554/eLife.21926

Share this article

https://doi.org/10.7554/eLife.21926

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