Developmentally regulated H2Av buffering via dynamic sequestration to lipid droplets in Drosophila embryos

Abstract

Regulating nuclear histone balance is essential for survival, yet in early Drosophila melanogaster embryos many regulatory strategies employed in somatic cells are unavailable. Previous work had suggested that lipid droplets (LDs) buffer nuclear accumulation of the histone variant H2Av. Here we elucidate the buffering mechanism and demonstrate that it is developmentally controlled. Using live imaging, we find that H2Av continuously exchanges between LDs. Our data suggest that the major driving force for H2Av accumulation in nuclei is H2Av abundance in the cytoplasm and that LD binding slows nuclear import kinetically, by limiting this cytoplasmic pool. Nuclear H2Av accumulation is indeed inversely regulated by overall buffering capacity. Histone exchange between LDs abruptly ceases during the midblastula transition, presumably to allow canonical regulatory mechanisms to take over. These findings provide a mechanistic basis for the emerging role of LDs as regulators of protein homeostasis and demonstrate that LDs can control developmental progression.

Data availability

All data generated or analyzed during this study are included in the manuscript.

Article and author information

Author details

  1. Matthew Richard Johnson

    Department of Biology, University of Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Roxan Amanda Stephenson

    Department of Biology, University of Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sina Ghaemmaghami

    Department of Biology, University of Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michael Andreas Welte

    Department of Biology, University of Rochester, Rochester, United States
    For correspondence
    michael.welte@rochester.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5741-4720

Funding

National Institutes of Health (RO1 GM102155)

  • Michael Andreas Welte

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

Reviewing Editor

  1. Robert V Farese, Harvard T. H. Chan School of Public Health, United States

Publication history

  1. Received: February 16, 2018
  2. Accepted: July 24, 2018
  3. Accepted Manuscript published: July 25, 2018 (version 1)
  4. Version of Record published: August 13, 2018 (version 2)

Copyright

© 2018, Johnson 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. Matthew Richard Johnson
  2. Roxan Amanda Stephenson
  3. Sina Ghaemmaghami
  4. Michael Andreas Welte
(2018)
Developmentally regulated H2Av buffering via dynamic sequestration to lipid droplets in Drosophila embryos
eLife 7:e36021.
https://doi.org/10.7554/eLife.36021

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