Eco1-dependent cohesin acetylation anchors chromatin loops and cohesion to define functional meiotic chromosome domains

  1. Rachael E Barton
  2. Lucia F Massari
  3. Daniel Robertson
  4. Adèle L Marston  Is a corresponding author
  1. University of Edinburgh, United Kingdom

Abstract

Cohesin organizes the genome by forming intra-chromosomal loops and inter-sister chromatid linkages. During gamete formation by meiosis, chromosomes are reshaped to support crossover recombination and two consecutive rounds of chromosome segregation. Here we show that meiotic chromosomes are organised into functional domains by Eco1 acetyltransferase-dependent positioning of both chromatin loops and sister chromatid cohesion in budding yeast. Eco1 acetylates the Smc3 cohesin subunit in meiotic S phase to establish chromatin boundaries, independently of DNA replication. Boundary formation by Eco1 is critical for prophase exit and for the maintenance of cohesion until meiosis II, but is independent of the ability of Eco1 to antagonize the cohesin-release factor, Wpl1. Conversely, prevention of cohesin release by Wpl1 is essential for centromeric cohesion, kinetochore monoorientation and co-segregation of sister chromatids in meiosis I. Our findings establish Eco1 as a key determinant of chromatin boundaries and cohesion positioning, revealing how local chromosome structuring directs genome transmission into gametes.

Data availability

Sequencing data has been deposited in GEO under accessions as below:* GSE185021 is the reference Series for your publication:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE185021* This SuperSeries record provides access to all of your data and is thebest accession to be quoted in any manuscript discussing the data. Forinformation on GEO linking and citing, please refer to:https://www.ncbi.nlm.nih.gov/geo/info/linking.html.* You may also cite the SubSeries that are linked to GSE185021:https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE185016https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE185017https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE185018https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE185019https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE185020

The following data sets were generated

Article and author information

Author details

  1. Rachael E Barton

    The Wellcome Centre for Cell Biology, Institute of 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:" 0000-0001-8553-9029
  2. Lucia F Massari

    The Wellcome Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  3. Daniel Robertson

    The Wellcome Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  4. Adèle L Marston

    The Wellcome Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    adele.marston@ed.ac.uk
    Competing interests
    Adèle L Marston, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3596-9407

Funding

Wellcome Trust (107827)

  • Rachael E Barton
  • Lucia F Massari
  • Adèle L Marston

Wellcome Trust (220780)

  • Lucia F Massari
  • Adèle L Marston

Wellcome Trust (102316)

  • Rachael E Barton

Wellcome Trust (203149)

  • Rachael E Barton
  • Lucia F Massari
  • Daniel Robertson
  • Adèle L Marston

Biotechnology and Biological Sciences Research Council (BB/S018018/1)

  • Rachael E Barton
  • Lucia F Massari
  • Adèle L Marston

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

Reviewing Editor

  1. Akira Shinohara, Osaka University, Japan

Publication history

  1. Preprint posted: September 25, 2021 (view preprint)
  2. Received: October 4, 2021
  3. Accepted: January 28, 2022
  4. Accepted Manuscript published: February 1, 2022 (version 1)
  5. Version of Record published: February 15, 2022 (version 2)

Copyright

© 2022, Barton 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.

Metrics

  • 1,007
    Page views
  • 197
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Rachael E Barton
  2. Lucia F Massari
  3. Daniel Robertson
  4. Adèle L Marston
(2022)
Eco1-dependent cohesin acetylation anchors chromatin loops and cohesion to define functional meiotic chromosome domains
eLife 11:e74447.
https://doi.org/10.7554/eLife.74447

Further reading

    1. Cell Biology
    Fangrui Chen et al.
    Research Article

    The major microtubule-organizing center (MTOC) in animal cells, the centrosome, comprises a pair of centrioles surrounded by pericentriolar material (PCM), which nucleates and anchors microtubules. Centrosome assembly depends on PCM binding to centrioles, PCM self-association and dynein-mediated PCM transport, but the self-assembly properties of PCM components in interphase cells are poorly understood. Here, we used experiments and modeling to study centriole-independent features of interphase PCM assembly. We showed that when centrioles are lost due to PLK4 depletion or inhibition, dynein-based transport and self-clustering of PCM proteins are sufficient to form a single compact MTOC, which generates a dense radial microtubule array. Interphase self-assembly of PCM components depends on γ-tubulin, pericentrin, CDK5RAP2 and ninein, but not NEDD1, CEP152 or CEP192. Formation of a compact acentriolar MTOC is inhibited by AKAP450-dependent PCM recruitment to the Golgi or by randomly organized CAMSAP2-stabilized microtubules, which keep PCM mobile and prevent its coalescence. Linking of CAMSAP2 to a minus-end-directed motor leads to the formation of an MTOC, but MTOC compaction requires cooperation with pericentrin-containing self-clustering PCM. Our data reveal that interphase PCM contains a set of components that can self-assemble into a compact structure and organize microtubules, but PCM self-organization is sensitive to motor- and microtubule-based rearrangement.

    1. Cell Biology
    2. Physics of Living Systems
    Danielle Holz et al.
    Research Article Updated

    Single molecule imaging has shown that part of actin disassembles within a few seconds after incorporation into the dendritic filament network in lamellipodia, suggestive of frequent destabilization near barbed ends. To investigate the mechanisms behind network remodeling, we created a stochastic model with polymerization, depolymerization, branching, capping, uncapping, severing, oligomer diffusion, annealing, and debranching. We find that filament severing, enhanced near barbed ends, can explain the single molecule actin lifetime distribution, if oligomer fragments reanneal to free ends with rate constants comparable to in vitro measurements. The same mechanism leads to actin networks consistent with measured filament, end, and branch concentrations. These networks undergo structural remodeling, leading to longer filaments away from the leading edge, at the +/-35° orientation pattern. Imaging of actin speckle lifetimes at sub-second resolution verifies frequent disassembly of newly-assembled actin. We thus propose a unified mechanism that fits a diverse set of basic lamellipodia phenomenology.