Lipid droplets buffer the histone supply of Drosophila embryos. Zhihuan Li, Michael Welte. Department of Biology, University of Rochester, Rochester, NY.

   In eukaryotic cells, DNA molecules wrap around histones to form nucleosomes, which protects the genome and regulates gene expression. However, excess free histones bind DNA randomly, alter nucleosome structure, interfere with gene expression, and ultimately cause cell lethality. Early Drosophila embryos contain massive amounts of excess histones H2A, H2B and H2Av. It has been hypothesized these excess histones are not detrimental to the embryo because they are sequestered on lipid droplets, fat storage organelles in the cytoplasm. We previously showed that the histones are bound to lipid droplets via the novel protein Jabba and serve as a backup supply that supports the rapid cell cycles of early embryogenesis. We now demonstrate that lipid droplets are not merely histone storage sites, but also protect the embryo from histone overexpression. In the wild type, we detect the overexpressed histones on lipid droplets, suggesting that lipid droplets can indeed bind and likely sequester supernumerary histones. In Jabba embryos, lipid droplets cannot recruit histones. In the nuclei of Jabba mutants, increased levels of histones accumulate during syncytial stages, presumably because they cannot be retained on lipid droplets and thus prematurely enter nuclei. In Jabba embryos, histone overexpression results in anaphase bridges, numerous mislocalized nuclei, abnormal morphology during cellularization, and embryonic lethality. We propose that lipid droplets serve as a buffer in the embryos, storing histones for the massive demands in early cell cycles and sequestering free histones to ensure genomic stability.