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

Elife. 2018 Jul 25;7:e36021. doi: 10.7554/eLife.36021.


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.

Keywords: D. melanogaster; Drosophila embryos; H2Av; cell biology; developmental biology; histones; lipid droplets; protein buffering.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Blastoderm / metabolism
  • Cell Nucleus / metabolism
  • Chromosomes / metabolism
  • Cytoplasmic Streaming
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics*
  • Embryo, Nonmammalian / metabolism*
  • Embryonic Development
  • Gene Dosage
  • Gene Expression Regulation, Developmental
  • Histones / genetics*
  • Histones / metabolism
  • Interphase
  • Kinetics
  • Lipid Droplets / metabolism*
  • Models, Biological


  • Drosophila Proteins
  • His2Av protein, Drosophila
  • Histones