title: Integration profiling of gene function with dense maps of transposon integration.
abstract: Understanding how complex networks of genes integrate to produce dividing cells is an important goal that is limited by the difficulty in defining the function of individual genes. Current resources for the systematic identification of gene function such as siRNA libraries and collections of deletion strains are costly and organism specific. We describe here integration profiling, a novel approach to identify the function of eukaryotic genes based upon dense maps of transposon integration. As a proof of concept, we used the transposon Hermes to generate a library of 360,513 insertions in the genome of Schizosaccharomyces pombe. On average, we obtained one insertion for every 29 bp of the genome. Hermes integrated more often into nucleosome free sites and 33% of the insertions occurred in ORFs. We found that ORFs with low integration densities successfully identified the genes that are essential for cell division. Importantly, the nonessential ORFs with intermediate levels of insertion correlated with the nonessential genes that have functions required for colonies to reach full size. This finding indicates that integration profiles can measure the contribution of nonessential genes to cell division. While integration profiling succeeded in identifying genes necessary for propagation, it also has the potential to identify genes important for many other functions such as DNA repair, stress response, and meiosis.
authors.affiliation: Section on Eukaryotic Transposable Elements, Program in Cellular Regulation and Metabolism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Guo
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Park
authors.forename: Bowen
authors.initials: B
authors.lastname: Cui
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Humes
authors.forename: Sunil
authors.initials: S
authors.lastname: Gangadharan
authors.forename: Stevephen
authors.initials: S
authors.lastname: Hung
authors.forename: Peter C
authors.initials: PC
authors.lastname: FitzGerald
authors.forename: Kwang-Lae
authors.initials: KL
authors.lastname: Hoe
authors.forename: Shiv I S
authors.initials: SI
authors.lastname: Grewal
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Craig
authors.forename: Henry L
authors.initials: HL
authors.lastname: Levin
mesh_terms: D002874:Chromosome Mapping; D004260:DNA Repair / Q000235:genetics; D004251:DNA Transposable Elements / Q000235:genetics*; D016678:Genome; D008540:Meiosis / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009707:Nucleosomes / Q000235:genetics*; D016366:Open Reading Frames; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements; D009707:Nucleosomes; D034741:RNA, Small Interfering
keywords: Hermes; Schizosaccharomyces pombe; Transposon; integration profile
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