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Defining genome architecture at base-pair resolution

Author

Listed:
  • Peng Hua

    (University of Oxford)

  • Mohsin Badat

    (University of Oxford)

  • Lars L. P. Hanssen

    (University of Oxford)

  • Lance D. Hentges

    (University of Oxford
    University of Oxford)

  • Nicholas Crump

    (University of Oxford)

  • Damien J. Downes

    (University of Oxford)

  • Danuta M. Jeziorska

    (University of Oxford)

  • A. Marieke Oudelaar

    (Max Planck Institute for Biophysical Chemistry)

  • Ron Schwessinger

    (University of Oxford
    University of Oxford)

  • Stephen Taylor

    (University of Oxford)

  • Thomas A. Milne

    (University of Oxford)

  • Jim R. Hughes

    (University of Oxford
    University of Oxford)

  • Doug R. Higgs

    (University of Oxford)

  • James O. J. Davies

    (University of Oxford)

Abstract

In higher eukaryotes, many genes are regulated by enhancers that are 104–106 base pairs (bp) away from the promoter. Enhancers contain transcription-factor-binding sites (which are typically around 7–22 bp), and physical contact between the promoters and enhancers is thought to be required to modulate gene expression. Although chromatin architecture has been mapped extensively at resolutions of 1 kilobase and above; it has not been possible to define physical contacts at the scale of the proteins that determine gene expression. Here we define these interactions in detail using a chromosome conformation capture method (Micro-Capture-C) that enables the physical contacts between different classes of regulatory elements to be determined at base-pair resolution. We find that highly punctate contacts occur between enhancers, promoters and CCCTC-binding factor (CTCF) sites and we show that transcription factors have an important role in the maintenance of the contacts between enhancers and promoters. Our data show that interactions between CTCF sites are increased when active promoters and enhancers are located within the intervening chromatin. This supports a model in which chromatin loop extrusion1 is dependent on cohesin loading at active promoters and enhancers, which explains the formation of tissue-specific chromatin domains without changes in CTCF binding.

Suggested Citation

  • Peng Hua & Mohsin Badat & Lars L. P. Hanssen & Lance D. Hentges & Nicholas Crump & Damien J. Downes & Danuta M. Jeziorska & A. Marieke Oudelaar & Ron Schwessinger & Stephen Taylor & Thomas A. Milne & , 2021. "Defining genome architecture at base-pair resolution," Nature, Nature, vol. 595(7865), pages 125-129, July.
  • Handle: RePEc:nat:nature:v:595:y:2021:i:7865:d:10.1038_s41586-021-03639-4
    DOI: 10.1038/s41586-021-03639-4
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    Cited by:

    1. Jinhua Dou & Chang Liu & Ruoyu Xiong & Hongguang Zhou & Guohua Lu & Liping Jia, 2022. "Empathy and Post-Traumatic Growth among Chinese Community Workers during the COVID-19 Pandemic: Roles of Self-Disclosure and Social Support," IJERPH, MDPI, vol. 19(23), pages 1-12, November.

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