Large domains of heterochromatin direct the formation of short mitotic chromosome loops

  1. Maximilian H Fitz-James
  2. Pin Tong
  3. Alison L Pidoux
  4. Hakan Ozadam
  5. Liyan Yang
  6. Sharon A White
  7. Job Dekker
  8. Robin Allshire  Is a corresponding author
  1. University of Edinburgh, United Kingdom
  2. University of Massachusetts Medical School, United States

Abstract

During mitosis chromosomes reorganise into highly compact, rod-shaped forms, thought to consist of consecutive chromatin loops around a central protein scaffold. Condensin complexes are involved in chromatin compaction, but the contribution of other chromatin proteins, DNA sequence and histone modifications is less understood. A large region of fission yeast DNA inserted into a mouse chromosome was previously observed to adopt a mitotic organisation distinct from that of surrounding mouse DNA. Here we show that a similar distinct structure is common to a large subset of insertion events in both mouse and human cells and is coincident with the presence of high levels of heterochromatic H3 lysine 9 trimethylation (H3K9me3). Hi-C and microscopy indicate that the heterochromatinised fission yeast DNA is organised into smaller chromatin loops than flanking euchromatic mouse chromatin. We conclude that heterochromatin alters chromatin loop size, thus contributing to the distinct appearance of heterochromatin on mitotic chromosomes.

Data availability

DNA sequencing and nanopore data were uploaded to the Sequence Read Archive with project ID PRJNA629899. Hi-C data was uploaded to GEO with accession ID GSE149677.

The following data sets were generated

Article and author information

Author details

  1. Maximilian H Fitz-James

    Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6084-5887
  2. Pin Tong

    Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  3. Alison L Pidoux

    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  4. Hakan Ozadam

    Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  5. Liyan Yang

    Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  6. Sharon A White

    Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  7. Job Dekker

    Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    Job Dekker, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5631-0698
  8. Robin Allshire

    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    robin.allshire@ed.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8005-3625

Funding

Wellcome Trust (Wellcome 4 year PhD studentship,102336/Z/13/Z)

  • Maximilian H Fitz-James

Wellcome Trust (Principal Research Fellowship,095021)

  • Robin Allshire

Wellcome Trust (Principal Research Fellowship,200885)

  • Robin Allshire

Wellcome Trust (Wellcome Centre for Cell Biology Core grant,203149)

  • Maximilian H Fitz-James
  • Pin Tong
  • Alison L Pidoux
  • Sharon A White
  • Robin Allshire

National Human Genome Research Institute (HG003143)

  • Hakan Ozadam
  • Liyan Yang
  • Job Dekker

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

Copyright

© 2020, Fitz-James 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. Maximilian H Fitz-James
  2. Pin Tong
  3. Alison L Pidoux
  4. Hakan Ozadam
  5. Liyan Yang
  6. Sharon A White
  7. Job Dekker
  8. Robin Allshire
(2020)
Large domains of heterochromatin direct the formation of short mitotic chromosome loops
eLife 9:e57212.
https://doi.org/10.7554/eLife.57212

Share this article

https://doi.org/10.7554/eLife.57212

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