Developmentally regulated H2Av buffering via dynamic sequestration to lipid droplets in Drosophila embryos
- University of Rochester, United States
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.
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All data generated or analyzed during this study are included in the manuscript.
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Author details
Michael Andreas Welte
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.
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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Developmentally regulated H2Av buffering via dynamic sequestration to lipid droplets in Drosophila embryos
eLife 7:e36021.
https://doi.org/10.7554/eLife.36021
