Cohesin architecture and clustering in vivo

  1. Siheng Xiang
  2. Douglas Koshland  Is a corresponding author
  1. University of California, Berkeley, United States

Abstract

Cohesin helps mediate sister chromatid cohesion, chromosome condensation, DNA repair and transcription regulation. We exploited proximity-dependent labeling to define the in vivo interactions of cohesin domains with DNA or with other cohesin domains that lie within the same or in different cohesin complexes. Our results suggest both cohesin's head and hinge domains bind to DNA, and cohesin structure is dynamic with differential folding of its coiled coil regions to generate butterfly confirmations. This method also reveals that cohesins form ordered clusters on and off DNA. The levels of cohesin clusters and their distribution on chromosomes are cell cycle-regulated. Cohesin clustering is likely necessary for cohesion maintenance because clustering and maintenance uniquely require the same subset of cohesin domains and the auxiliary cohesin factor Pds5p. These conclusions provide important new mechanistic and biological insights into the architecture of the cohesin complex, cohesin-cohesin interactions, and cohesin's tethering and loop extruding activities.

Data availability

Sequencing data have been deposited in GEO as GSE157155.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Siheng Xiang

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Douglas Koshland

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    koshland@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3742-6294

Funding

Helen Hay Whitney Foundation

  • Siheng Xiang

National Institute of General Medical Sciences (1R35 GM-118189-01)

  • Douglas Koshland

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

Copyright

© 2021, Xiang & Koshland

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

  • 2,769
    views
  • 480
    downloads
  • 32
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Siheng Xiang
  2. Douglas Koshland
(2021)
Cohesin architecture and clustering in vivo
eLife 10:e62243.
https://doi.org/10.7554/eLife.62243

Share this article

https://doi.org/10.7554/eLife.62243

Further reading

    1. Chromosomes and Gene Expression
    Shihui Chen, Carolyn Marie Phillips
    Research Article

    RNA interference (RNAi) is a conserved pathway that utilizes Argonaute proteins and their associated small RNAs to exert gene regulatory function on complementary transcripts. While the majority of germline-expressed RNAi proteins reside in perinuclear germ granules, it is unknown whether and how RNAi pathways are spatially organized in other cell types. Here, we find that the small RNA biogenesis machinery is spatially and temporally organized during Caenorhabditis elegans embryogenesis. Specifically, the RNAi factor, SIMR-1, forms visible concentrates during mid-embryogenesis that contain an RNA-dependent RNA polymerase, a poly-UG polymerase, and the unloaded nuclear Argonaute protein, NRDE-3. Curiously, coincident with the appearance of the SIMR granules, the small RNAs bound to NRDE-3 switch from predominantly CSR-class 22G-RNAs to ERGO-dependent 22G-RNAs. NRDE-3 binds ERGO-dependent 22G-RNAs in the somatic cells of larvae and adults to silence ERGO-target genes; here we further demonstrate that NRDE-3-bound, CSR-class 22G-RNAs repress transcription in oocytes. Thus, our study defines two separable roles for NRDE-3, targeting germline-expressed genes during oogenesis to promote global transcriptional repression, and switching during embryogenesis to repress recently duplicated genes and retrotransposons in somatic cells, highlighting the plasticity of Argonaute proteins and the need for more precise temporal characterization of Argonaute-small RNA interactions.

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics
    Steven Henikoff, David L Levens
    Insight

    A new method for mapping torsion provides insights into the ways that the genome responds to the torsion generated by RNA polymerase II.