Project description:DAF-12 is involved in development, dauer formation, and aging in Caenorhabditis elegans. To understand how DAF-12 is involved in these biologic processes, we performed chIP-chip using a DAF-12:TAP transgene and an anti-DAF-12 antibody. We identified 1175 genomic binding sites which were located within 5 kb of 3179 genes. These genes include known DAF-12 target genes as well as new genes involved in developmental timing, microRNA function, and stress resistance. The supplemental BED file contains all 1175 genomic binding sites described in our work.
Project description:To identify DAF-16-dependent transcriptional alterations that occur in a long-lived C. elegans strain, we used cDNA microarrays and genomic analysis to identify putative direct and indirect DAF-16 transcriptional target genes. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
Project description:Insulin/IGF-1 Signaling (IIS) is known to constrain longevity by inhibiting the transcription factor FOXO. How phosphorylation mediated by IIS kinases regulates lifespan beyond FOXO remains unclear. Here, we profile IIS-dependent phosphorylation changes in a large-scale quantitative phosphoproteomic analysis of wild-type and three IIS mutant Caenorhabditis elegans strains. We quantify more than 15,000 phosphosites and find that 476 of these are differentially phosphorylated in the long-lived daf-2/insulin receptor mutant. We develop a machine learning-based method to prioritize 25 potential lifespan-related phosphosites. We perform validations to show that AKT-1 pT492 inhibits DAF-16/FOXO and compensates the loss of daf-2 function, that EIF-2α pS49 potently inhibits protein synthesis and daf-2 longevity, and that reduced phosphorylation of multiple germline proteins apparently transmits reduced DAF-2 signaling to the soma. In addition, an analysis of kinases with enriched substrates detects that casein kinase 2 (CK2) subunits negatively regulate lifespan. Our study reveals detailed functional insights into longevity.
