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High-resolution targeted 3C interrogation of cis-regulatory element organization at genome-wide scale

Author

Listed:
  • Damien J. Downes

    (University of Oxford)

  • Robert A. Beagrie

    (University of Oxford)

  • Matthew E. Gosden

    (University of Oxford)

  • Jelena Telenius

    (University of Oxford)

  • Stephanie J. Carpenter

    (University of Oxford)

  • Lea Nussbaum

    (University of Oxford)

  • Sara Ornellas

    (University of Oxford
    University of Oxford)

  • Martin Sergeant

    (University of Oxford)

  • Chris Q. Eijsbouts

    (Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford
    University of Oxford)

  • Ron Schwessinger

    (University of Oxford
    University of Oxford)

  • Jon Kerry

    (University of Oxford)

  • Nigel Roberts

    (University of Oxford)

  • Arun Shivalingam

    (University of Oxford)

  • Afaf El-Sagheer

    (University of Oxford)

  • A. Marieke Oudelaar

    (University of Oxford
    University of Oxford)

  • Tom Brown

    (University of Oxford)

  • Veronica J. Buckle

    (University of Oxford)

  • James O. J. Davies

    (University of Oxford)

  • Jim R. Hughes

    (University of Oxford
    University of Oxford)

Abstract

Chromosome conformation capture (3C) provides an adaptable tool for studying diverse biological questions. Current 3C methods generally provide either low-resolution interaction profiles across the entire genome, or high-resolution interaction profiles at limited numbers of loci. Due to technical limitations, generation of reproducible high-resolution interaction profiles has not been achieved at genome-wide scale. Here, to overcome this barrier, we systematically test each step of 3C and report two improvements over current methods. We show that up to 30% of reporter events generated using the popular in situ 3C method arise from ligations between two individual nuclei, but this noise can be almost entirely eliminated by isolating intact nuclei after ligation. Using Nuclear-Titrated Capture-C, we generate reproducible high-resolution genome-wide 3C interaction profiles by targeting 8055 gene promoters in erythroid cells. By pairing high-resolution 3C interaction calls with nascent gene expression we interrogate the role of promoter hubs and super-enhancers in gene regulation.

Suggested Citation

  • Damien J. Downes & Robert A. Beagrie & Matthew E. Gosden & Jelena Telenius & Stephanie J. Carpenter & Lea Nussbaum & Sara Ornellas & Martin Sergeant & Chris Q. Eijsbouts & Ron Schwessinger & Jon Kerry, 2021. "High-resolution targeted 3C interrogation of cis-regulatory element organization at genome-wide scale," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20809-6
    DOI: 10.1038/s41467-020-20809-6
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    Cited by:

    1. Joyce J. Thompson & Daniel J. Lee & Apratim Mitra & Sarah Frail & Ryan K. Dale & Pedro P. Rocha, 2022. "Extensive co-binding and rapid redistribution of NANOG and GATA6 during emergence of divergent lineages," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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