Lipid Droplets Control the Maternal Histone Supply of Drosophila Embryos

Abstract

Summary Background Histones are essential for chromatin packing, yet free histones not incorporated into chromatin are toxic. While in most cells multiple regulatory mechanisms prevent accumulation of excess histones, early Drosophila embryos contain massive extra-nuclear histone stores, thought to be essential for development. Excess histones H2A, H2B, and H2Av are bound to lipid droplets, ubiquitous fat storage organelles especially abundant in embryos. It has been proposed that sequestration on lipid droplets allows safe transient storage of supernumerary histones. Results Here we critically test this sequestration hypothesis. We find that histones are anchored to lipid droplets via the previously uncharacterized protein Jabba: Jabba localizes to droplets, co-immunoprecipitates with histones, and is necessary to recruit histones to droplets. Jabba mutants lack the maternal H2A, H2B, and H2Av deposits altogether; presumably, these deposits are eliminated unless sequestered on droplets. Jabba mutant embryos compensate for this histone deficit by translating maternal histone mRNAs. However, when histone expression is mildly compromised, the maternal histone protein deposits are essential for proper early mitoses and for viability. Conclusions A growing number of proteins from other cellular compartments have been found to transiently associate with lipid droplets. Our studies provide the first insight into mechanism and functional relevance of this sequestration. We conclude that sequestration on lipid droplets allows embryos to build up extra-nuclear histones stores and provides histones for chromatin assembly during times of high demand. This work reveals a novel aspect of histone metabolism and establishes lipid droplets as functional storage sites for unstable or detrimental proteins.

A novel role for lipid droplets in the organismal antibacterial response

“…We employed two mutant alleles of Jabba (also known as CG42351): Jabba zl01 is a promoter deletion and expresses no Jabba protein in early embryos; Jabba f07560 is a transposable element insertion between two coding exons of Jabba , resulting in a severely truncated Jabba protein. A comprehensive molecular and phenotypic description of Jabba mutant alleles will be published elsewhere (Li et al, 2012). Alleles Jabba zl01 and Jabba f07560 were derived independently, and thus likely share few, if any, unknown secondary mutations.…”

Arabidopsis Small Rubber Particle Protein Homolog SRPs Play Dual Roles as Positive Factors for Tissue Growth and Development and in Drought Stress Responses

“…An additional property of LDs as a protein-storage depot is that they store extra-nuclear histones and may provide histones to the nuclei for efficient chromatin assembly during times of high demand (Cermelli et al, 2006;Li et al, 2012). Spatiotemporal regulation of histones by LDs may control the expression of a subset of genes during cellular proliferation and in response to stress, which in turn, increases tissue growth and tolerance against stress such as drought.…”

Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation

“…Droplets of Drosophila early embryos store certain histones through an interaction with the droplet surface protein Jabba. In the absence of Jabba, the histones are degraded (Cermelli et al, 2006;Li et al, 2012Li et al, , 2014, suggesting that lipid droplets not only store lipid precursors but also can supply histones for rapid chromatin remodeling.…”