<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Nuclear positioning and a non-uniform metabolism exert epigenetic control of gene expression in the wing disc"^^ . "In my PhD project, I used the pseudostratified epithelium of the wing imaginal disc of Drosophila melanogaster as a model system to study the significance of cellular metabolism and nuclear positioning for tissue development in vivo. The wing disc is a larval precursor tissue that mainly gives rise to the adult wing. It is surrounded by the larval hemolymph, providing metabolites, such as lipoprotein-bound lipids. As a read-out for the metabolic state of the wing disc, I investigated the disc epigenome as most histone modifying and demodifying enzymes require metabolic co-factors or substrates. In this study, I identified a nonuniform distribution of histone acetylation in the wing disc with high acetylation levels specifically in nuclei facing the tissue surface. This rim pattern is not defined by cell cycle or cellular identity but by the position of the nucleus within the tissue. Accordingly, genetic ablation of the disc rim causes the formation of a new rim with high histone acetylation in the remaining, now outward facing, tissue region. High acetylation levels in nuclei in the disc rim correlate with hemolymph-exposure as indicated by accumulation of lipoproteins on outwardfacing membranes. The acetylation pattern persists during wing disc development suggesting a continuous regulatory role in tissue growth. The non-uniform distribution of histone acetylation is achieved by local activity of the acetyltransferase nejire in the rim of the disc. Spatially restricted nejire activity in the rim is not determined by non-uniform intrinsic activity or expression of the enzyme but by local availability of its metabolic substrate acetyl-CoA. Required acetyl-CoA is specifically generated in outward-facing nuclei due to increased levels of nuclear acetyl-CoA synthase which converts acetate to acetyl-CoA. Metabolically, this rim acetylation pattern depends on acetate derived from fatty acid β-oxidation, which is also nonuniform and increased in the rim of the wing disc, as evidenced by a high mitochondrial membrane potential in this tissue region. Rim histone acetylation epigenetically impacts expression of genes in the wing disc implicated in developmentally important signaling pathways, including Hippo, Notch, and Hedgehog. Jointly, my findings suggest a novel role for nuclear positioning and a concordantly aligned metabolism in determining cell fate and, consequently, wing disc development."^^ . "2023" . . . . . . . "Philipp"^^ . "Willnow"^^ . "Philipp Willnow"^^ . . . . . . "Nuclear positioning and a non-uniform metabolism exert epigenetic control of gene expression in the wing disc (PDF)"^^ . . . "PhD_thesis_Philipp_Willnow.pdf"^^ . . . "Nuclear positioning and a non-uniform metabolism exert epigenetic control of gene expression in the wing disc (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Nuclear positioning and a non-uniform metabolism exert epigenetic control of gene expression in the wing disc (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Nuclear positioning and a non-uniform metabolism exert epigenetic control of gene expression in the wing disc (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Nuclear positioning and a non-uniform metabolism exert epigenetic control of gene expression in the wing disc (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Nuclear positioning and a non-uniform metabolism exert epigenetic control of gene expression in the wing disc (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #20417 \n\nNuclear positioning and a non-uniform metabolism exert epigenetic control of gene expression in the wing disc\n\n" . "text/html" . . . "000 Allgemeines, Wissenschaft, Informatik"@de . "000 Generalities, Science"@en . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . . . "610 Medizin"@de . "610 Medical sciences Medicine"@en . .