Nuclear position and local acetyl-CoA production regulate chromatin state.

Histone acetylation regulates gene expression, cell function and cell fate1. Here we study the pattern of histone acetylation in the epithelial tissue of the Drosophila wing disc. H3K18ac, H4K8ac and total lysine acetylation are increased in the outer rim of the disc. This acetylation pattern is controlled by nuclear position, whereby nuclei continuously move from apical to basal locations within the epithelium and exhibit high levels of H3K18ac when they are in proximity to the tissue surface. These surface nuclei have increased levels of acetyl-CoA synthase, which generates the acetyl-CoA for histone acetylation. The carbon source for histone acetylation in the rim is fatty acid ß-oxidation, which is also increased in the rim. Inhibition of fatty acid ß-oxidation causes H3K18ac levels to decrease in the genomic proximity of genes involved in disc development. In summary, there is a physical mark of the outer rim of the wing and other imaginal epithelia in Drosophila that affects gene expression.

Metabolites Regulate Cell Signaling and Growth via Covalent Modification of Proteins.

Metabolites affect cell growth in two different ways. First, they serve as building blocks for biomass accumulation. Second, metabolites regulate the activity of growth-relevant signaling pathways. They do so in part by covalently attaching to proteins, thereby generating post-translational modifications (PTMs) that affect protein function, the focus of this Perspective. Recent advances in mass spectrometry have revealed a wide variety of such metabolites, including lipids, amino acids, Coenzyme-A, acetate, malonate, and lactate to name a few. An active area of research is to understand which modifications affect protein function and how they do so. In many cases, the cellular levels of these metabolites affect the stoichiometry of the corresponding PTMs, providing a direct link between cell metabolism and the control of cell signaling, transcription, and cell growth.

Gene expression atlas of a developing tissue by single cell expression correlation analysis.

The Drosophila wing disc has been a fundamental model system for the discovery of key signaling pathways and for our understanding of developmental processes. However, a complete map of gene expression in this tissue is lacking. To obtain a gene expression atlas in the wing disc, we employed single cell RNA sequencing (scRNA-seq) and developed a method for analyzing scRNA-seq data based on gene expression correlations rather than cell mapping. This enables us to compute expression maps for all detected genes in the wing disc and to discover 824 genes with spatially restricted expression patterns. This approach identifies clusters of genes with similar expression patterns and functional relevance. As proof of concept, we characterize the previously unstudied gene CG5151 and show that it regulates Wnt signaling. Our method will enable the leveraging of scRNA-seq data for generating expression atlases of undifferentiated tissues during development.