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Chromosomal coordination and differential structure of asynchronous replicating regions

Author

Listed:
  • Britny Blumenfeld

    (IMRIC, Hebrew University Medical School)

  • Hagit Masika

    (Hebrew University Medical School)

  • Marganit Farago

    (Hebrew University Medical School)

  • Yishai Yehuda

    (IMRIC, Hebrew University Medical School
    Jerusalem College of Technology)

  • Lamia Halaseh

    (Hebrew University Medical School)

  • Oriya Vardi

    (Hebrew University Medical School)

  • Rachel Rapoport

    (IMRIC, Hebrew University Medical School)

  • Rena Levin-Klein

    (Hebrew University Medical School)

  • Howard Cedar

    (Hebrew University Medical School)

  • Yehudit Bergman

    (Hebrew University Medical School)

  • Itamar Simon

    (IMRIC, Hebrew University Medical School)

Abstract

Stochastic asynchronous replication timing (AS-RT) is a phenomenon in which the time of replication of each allele is different, and the identity of the early allele varies between cells. By taking advantage of stable clonal pre-B cell populations derived from C57BL6/Castaneous mice, we have mapped the genome-wide AS-RT loci, independently of genetic differences. These regions are characterized by differential chromatin accessibility, mono-allelic expression and include new gene families involved in specifying cell identity. By combining population level mapping with single cell FISH, our data reveal the existence of a novel regulatory program that coordinates a fixed relationship between AS-RT regions on any given chromosome, with some loci set to replicate in a parallel and others set in the anti-parallel orientation. Our results show that AS-RT is a highly regulated epigenetic mark established during early embryogenesis that may be used for facilitating the programming of mono-allelic choice throughout development.

Suggested Citation

  • Britny Blumenfeld & Hagit Masika & Marganit Farago & Yishai Yehuda & Lamia Halaseh & Oriya Vardi & Rachel Rapoport & Rena Levin-Klein & Howard Cedar & Yehudit Bergman & Itamar Simon, 2021. "Chromosomal coordination and differential structure of asynchronous replicating regions," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21348-4
    DOI: 10.1038/s41467-021-21348-4
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    Cited by:

    1. Michelle Dietzen & Haoran Zhai & Olivia Lucas & Oriol Pich & Christopher Barrington & Wei-Ting Lu & Sophia Ward & Yanping Guo & Robert E. Hynds & Simone Zaccaria & Charles Swanton & Nicholas McGranaha, 2024. "Replication timing alterations are associated with mutation acquisition during breast and lung cancer evolution," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    2. Michael B. Heskett & Athanasios E. Vouzas & Leslie G. Smith & Phillip A. Yates & Christopher Boniface & Eric E. Bouhassira & Paul T. Spellman & David M. Gilbert & Mathew J. Thayer, 2022. "Epigenetic control of chromosome-associated lncRNA genes essential for replication and stability," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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