RESUMEN
Histone H2A monoubiquitylation (H2Aub) is considered to be a key effector in transcriptional repression by Polycomb-repressive complex 1 (PRC1). We analyzed Drosophila with a point mutation in the PRC1 subunit Sce that abolishes its H2A ubiquitylase activity or with point mutations in the H2A and H2Av residues ubiquitylated by PRC1. H2Aub is essential for viability and required for efficient histone H3 Lys27 trimethylation by PRC2 early in embryogenesis. However, H2Aub-deficient animals fully maintain repression of PRC1 target genes and do not show phenotypes characteristic of Polycomb group mutants. PRC1 thus represses canonical target genes independently of H2Aub.
Asunto(s)
Proteínas de Drosophila , Drosophila/embriología , Drosophila/genética , Regulación del Desarrollo de la Expresión Génica , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Animales , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulación del Desarrollo de la Expresión Génica/genética , Histonas/genética , Histonas/metabolismo , Metamorfosis Biológica/genética , Mutación , Ubiquitina-Proteína Ligasas/metabolismo , UbiquitinaciónRESUMEN
Early-life nourishment exerts long-term influences upon adult physiology and disease risk. These lasting effects of diet are well established but the underlying mechanisms are only partially understood. Here we show that restricting dietary yeast during Drosophila development can, depending upon the subsequent adult environment, more than double median lifespan. Developmental diet acts via a long-term influence upon the adult production of toxic molecules, which we term autotoxins, that are shed into the environment and shorten the lifespan of both sexes. Autotoxins are synthesised by oenocytes and some of them correspond to alkene hydrocarbons that also act as pheromones. This study identifies a mechanism by which the developmental dietary history of an animal regulates its own longevity and that of its conspecific neighbours. It also has important implications for the design of lifespan experiments as autotoxins can influence the regulation of longevity by other factors including diet, sex, insulin signalling and population density.
Asunto(s)
Alquenos/metabolismo , Dieta , Drosophila melanogaster/fisiología , Longevidad/fisiología , Alquenos/química , Animales , Animales Modificados Genéticamente , Drosophila melanogaster/citología , Femenino , Vivienda para Animales , Insulina/metabolismo , Larva/crecimiento & desarrollo , Metabolismo de los Lípidos/fisiología , MasculinoRESUMEN
Although many metazoan enzymes that add or remove specific modifications on histone proteins are essential transcriptional regulators, the functional significance of posttranslational modifications on histone proteins is not well understood. Here, we show in Drosophila that a point mutation in lysine 27 of histone H3 (H3-K27) fails to repress transcription of genes that are normally repressed by Polycomb repressive complex 2 (PRC2), the methyltransferase that modifies H3-K27. Moreover, differentiated H3-K27 mutant cells show homeotic transformations like those seen in PRC2 mutant cells. Taken together, these analyses demonstrate that H3-K27 is the crucial physiological substrate that PRC2 modifies for Polycomb repression.