Archaeal chromatin 'slinkies' are inherently dynamic complexes with deflected DNA wrapping pathways

  1. Samuel Bowerman
  2. Jeff Wereszczynski
  3. Karolin Luger  Is a corresponding author
  1. HHMI and University of Colorado, Boulder, United States
  2. Illinois Institute of Technology, United States

Abstract

Eukaryotes and many archaea package their DNA with histones. While the four eukaryotic histones wrap ~147 DNA base pairs into nucleosomes, archaeal histones form 'nucleosome-like' complexes that continuously wind between 60 - 500 base pairs of DNA ('archaeasomes'), suggested by crystal contacts and analysis of cellular chromatin. Solution structures of large archaeasomes (>90 DNA base pairs) have never been directly observed. Here, we utilize molecular dynamics simulations, analytical ultracentrifugation, and cryoEM to structurally characterize the solution state of archaeasomes on longer DNA. Simulations reveal dynamics of increased accessibility without disruption of DNA-binding or tetramerization interfaces. Mg2+ concentration influences compaction, and cryoEM densities illustrate that DNA is wrapped in consecutive substates arranged 90o out-of-plane with one another. Without ATP-dependent remodelers, archaea may leverage these inherent dynamics to balance chromatin packing and accessibility.

Data availability

cryoEM datasets have been uploaded to EMPIAR (EMD-23403, EMD-23404). The pdb files are submitted as supplementary information. MD trajectories will be stored on CU storage resources (PetaLibrary) and made available upon request through file transfer or shipping of external hard drives.

Article and author information

Author details

  1. Samuel Bowerman

    Department of Chemistry and Biochemistry, HHMI and University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jeff Wereszczynski

    Department of Physics, Illinois Institute of Technology, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Karolin Luger

    Department of Chemistry and Biochemistry, HHMI and University of Colorado, Boulder, Boulder, United States
    For correspondence
    karolin.luger@colorado.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5136-5331

Funding

National Science Foundation (1552743)

  • Jeff Wereszczynski

National Institute of General Medical Sciences (R35GM119647)

  • Jeff Wereszczynski

Howard Hughes Medical Institute (NA)

  • Karolin Luger

National Institute of General Medical Sciences (F32GM137496)

  • Samuel Bowerman

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

Reviewing Editor

  1. Sebastian Deindl, Uppsala University, Sweden

Version history

  1. Received: December 9, 2020
  2. Accepted: February 16, 2021
  3. Accepted Manuscript published: March 2, 2021 (version 1)
  4. Version of Record published: March 24, 2021 (version 2)

Copyright

© 2021, Bowerman 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

  • 5,918
    views
  • 764
    downloads
  • 38
    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. Samuel Bowerman
  2. Jeff Wereszczynski
  3. Karolin Luger
(2021)
Archaeal chromatin 'slinkies' are inherently dynamic complexes with deflected DNA wrapping pathways
eLife 10:e65587.
https://doi.org/10.7554/eLife.65587

Share this article

https://doi.org/10.7554/eLife.65587

Further reading

    1. Chromosomes and Gene Expression
    Marwan Anoud, Emmanuelle Delagoutte ... Jean-Paul Concordet
    Research Article

    Tardigrades are microscopic animals renowned for their ability to withstand extreme conditions, including high doses of ionizing radiation (IR). To better understand their radio-resistance, we first characterized induction and repair of DNA double- and single-strand breaks after exposure to IR in the model species Hypsibius exemplaris. Importantly, we found that the rate of single-strand breaks induced was roughly equivalent to that in human cells, suggesting that DNA repair plays a predominant role in tardigrades’ radio-resistance. To identify novel tardigrade-specific genes involved, we next conducted a comparative transcriptomics analysis across three different species. In all three species, many DNA repair genes were among the most strongly overexpressed genes alongside a novel tardigrade-specific gene, which we named Tardigrade DNA damage Response 1 (TDR1). We found that TDR1 protein interacts with DNA and forms aggregates at high concentration suggesting it may condensate DNA and preserve chromosome organization until DNA repair is accomplished. Remarkably, when expressed in human cells, TDR1 improved resistance to Bleomycin, a radiomimetic drug. Based on these findings, we propose that TDR1 is a novel tardigrade-specific gene conferring resistance to IR. Our study sheds light on mechanisms of DNA repair helping cope with high levels of DNA damage inflicted by IR.

    1. Chromosomes and Gene Expression
    Joshua D Eaton, Jessica Board ... Steven West
    Short Report

    RNA polymerase II (RNAPII) transcription initiates bidirectionally at many human protein-coding genes. Sense transcription usually dominates and leads to messenger RNA production, whereas antisense transcription rapidly terminates. The basis for this directionality is not fully understood. Here, we show that sense transcriptional initiation is more efficient than in the antisense direction, which establishes initial promoter directionality. After transcription begins, the opposing functions of the endonucleolytic subunit of Integrator, INTS11, and cyclin-dependent kinase 9 (CDK9) maintain directionality. Specifically, INTS11 terminates antisense transcription, whereas sense transcription is protected from INTS11-dependent attenuation by CDK9 activity. Strikingly, INTS11 attenuates transcription in both directions upon CDK9 inhibition, and the engineered recruitment of CDK9 desensitises transcription to INTS11. Therefore, the preferential initiation of sense transcription and the opposing activities of CDK9 and INTS11 explain mammalian promoter directionality.