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Dynamics of the 4D genome during in vivo lineage specification and differentiation

Author

Listed:
  • A. Marieke Oudelaar

    (University of Oxford
    University of Oxford)

  • Robert A. Beagrie

    (University of Oxford)

  • Matthew Gosden

    (University of Oxford)

  • Sara Ornellas

    (University of Oxford
    University of Oxford)

  • Emily Georgiades

    (University of Oxford
    University of Oxford)

  • Jon Kerry

    (University of Oxford)

  • Daniel Hidalgo

    (University of Massachusetts Medical School Worcester)

  • Joana Carrelha

    (University of Oxford)

  • Arun Shivalingam

    (University of Oxford)

  • Afaf H. El-Sagheer

    (University of Oxford
    Faculty of Petroleum and Mining Engineering, Suez University)

  • Jelena M. Telenius

    (University of Oxford
    University of Oxford)

  • Tom Brown

    (University of Oxford)

  • Veronica J. Buckle

    (University of Oxford)

  • Merav Socolovsky

    (University of Massachusetts Medical School Worcester)

  • Douglas R. Higgs

    (University of Oxford)

  • Jim R. Hughes

    (University of Oxford
    University of Oxford)

Abstract

Mammalian gene expression patterns are controlled by regulatory elements, which interact within topologically associating domains (TADs). The relationship between activation of regulatory elements, formation of structural chromatin interactions and gene expression during development is unclear. Here, we present Tiled-C, a low-input chromosome conformation capture (3C) technique. We use this approach to study chromatin architecture at high spatial and temporal resolution through in vivo mouse erythroid differentiation. Integrated analysis of chromatin accessibility and single-cell expression data shows that regulatory elements gradually become accessible within pre-existing TADs during early differentiation. This is followed by structural re-organization within the TAD and formation of specific contacts between enhancers and promoters. Our high-resolution data show that these enhancer-promoter interactions are not established prior to gene expression, but formed gradually during differentiation, concomitant with progressive upregulation of gene activity. Together, these results provide new insight into the close, interdependent relationship between chromatin architecture and gene regulation during development.

Suggested Citation

  • A. Marieke Oudelaar & Robert A. Beagrie & Matthew Gosden & Sara Ornellas & Emily Georgiades & Jon Kerry & Daniel Hidalgo & Joana Carrelha & Arun Shivalingam & Afaf H. El-Sagheer & Jelena M. Telenius &, 2020. "Dynamics of the 4D genome during in vivo lineage specification and differentiation," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16598-7
    DOI: 10.1038/s41467-020-16598-7
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    Cited by:

    1. Laureano Tomás-Daza & Llorenç Rovirosa & Paula López-Martí & Andrea Nieto-Aliseda & François Serra & Ainoa Planas-Riverola & Oscar Molina & Rebecca McDonald & Cedric Ghevaert & Esther Cuatrecasas & Do, 2023. "Low input capture Hi-C (liCHi-C) identifies promoter-enhancer interactions at high-resolution," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Abrar Aljahani & Peng Hua & Magdalena A. Karpinska & Kimberly Quililan & James O. J. Davies & A. Marieke Oudelaar, 2022. "Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. D. M. Jeziorska & E. A. J. Tunnacliffe & J. M. Brown & H. Ayyub & J. Sloane-Stanley & J. A. Sharpe & B. C. Lagerholm & C. Babbs & A. J. H. Smith & V. J. Buckle & D. R. Higgs, 2022. "On-microscope staging of live cells reveals changes in the dynamics of transcriptional bursting during differentiation," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Dominic D. G. Owens & Giorgio Anselmi & A. Marieke Oudelaar & Damien J. Downes & Alessandro Cavallo & Joe R. Harman & Ron Schwessinger & Akin Bucakci & Lucas Greder & Sara Ornellas & Danuta Jeziorska , 2022. "Dynamic Runx1 chromatin boundaries affect gene expression in hematopoietic development," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Grigorios Georgolopoulos & Nikoletta Psatha & Mineo Iwata & Andrew Nishida & Tannishtha Som & Minas Yiangou & John A. Stamatoyannopoulos & Jeff Vierstra, 2021. "Discrete regulatory modules instruct hematopoietic lineage commitment and differentiation," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

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