1. Computational and Systems Biology
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A new experimental platform facilitates assessment of the transcriptional and chromatin landscapes of aging yeast

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Cite this article as: eLife 2018;7:e39911 doi: 10.7554/eLife.39911

Abstract

Replicative aging of Saccharomyces cerevisiae is an established model system for eukaryotic cellular aging. A limitation in yeast lifespan studies has been the difficulty of separating old cells from young cells in large quantities. We engineered a new platform, the Miniature-chemostat Aging Device (MAD), that enables purification of aged cells at sufficient quantities for genomic and biochemical characterization of aging yeast populations. Using MAD, we measured DNA accessibility and gene expression changes in aging cells. Our data highlight an intimate connection between aging, growth rate, and stress. Stress-independent genes that change with age are highly enriched for targets of the signal recognition particle (SRP). Combining MAD with an improved ATAC-Seq method, we find that increasing proteasome activity reduces rDNA instability usually observed in aging cells, and contrary to published findings, provide evidence that global nucleosome occupancy does not change significantly with age.

Article and author information

Author details

  1. David G Hendrickson

    Calico Life Sciences, LLC, South San Francisco, United States
    Competing interests
    David G Hendrickson, Is affiliated with Calico Life Sciences. There are no other competing interests.
  2. Ilya Soifer

    Calico Life Sciences, LLC, South San Francisco, United States
    Competing interests
    Ilya Soifer, Is affiliated with Calico Life Sciences. There are no other competing interests.
  3. Bernd J Wranik

    Calico Life Sciences, LLC, South San Francisco, United States
    Competing interests
    Bernd J Wranik, Is affiliated with Calico Life Sciences. There are no other competing interests.
  4. Griffin Kim

    Calico Life Sciences, LLC, South San Francisco, United States
    Competing interests
    Griffin Kim, Is affiliated with Calico Life Sciences. There are no other competing interests.
  5. Michael Robles

    Calico Life Sciences, LLC, South San Francisco, United States
    Competing interests
    Michael Robles, Is affiliated with Calico Life Sciences. There are no other competing interests.
  6. Patrick A Gibney

    Calico Life Sciences, LLC, South San Francisco, United States
    Competing interests
    Patrick A Gibney, Is affiliated with Calico Life Sciences. There are no other competing interests.
  7. R Scott McIsaac

    Calico Life Sciences, LLC, South San Francisco, United States
    For correspondence
    rsm@calicolabs.com
    Competing interests
    R Scott McIsaac, Is affiliated with Calico Life Sciences. There are no other competing interests.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5339-6032

Funding

The authors declare that there was no funding for this work.

Reviewing Editor

  1. Matt Kaeberlein, University of Washington, United States

Publication history

  1. Received: July 18, 2018
  2. Accepted: October 17, 2018
  3. Accepted Manuscript published: October 18, 2018 (version 1)
  4. Accepted Manuscript updated: October 19, 2018 (version 2)
  5. Version of Record published: November 28, 2018 (version 3)

Copyright

© 2018, Hendrickson 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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