排序方式: 共有125条查询结果,搜索用时 15 毫秒
51.
Ryan CJ Roguev A Patrick K Xu J Jahari H Tong Z Beltrao P Shales M Qu H Collins SR Kliegman JI Jiang L Kuo D Tosti E Kim HS Edelmann W Keogh MC Greene D Tang C Cunningham P Shokat KM Cagney G Svensson JP Guthrie C Espenshade PJ Ideker T Krogan NJ 《Molecular cell》2012,46(5):691-704
To date, cross-species comparisons of genetic interactomes have been restricted to small or functionally related gene sets, limiting our ability to infer evolutionary trends. To facilitate a more comprehensive analysis, we constructed a genome-scale epistasis map (E-MAP) for the fission yeast Schizosaccharomyces pombe, providing phenotypic signatures for ~60% of the nonessential genome. Using these signatures, we generated a catalog of 297 functional modules, and we assigned function to 144 previously uncharacterized genes, including mRNA splicing and DNA damage checkpoint factors. Comparison with an integrated genetic interactome from the budding yeast Saccharomyces cerevisiae revealed a hierarchical model for the evolution of genetic interactions, with conservation highest within protein complexes, lower within biological processes, and lowest between distinct biological processes. Despite the large evolutionary distance and extensive rewiring of individual interactions, both networks retain conserved features and display similar levels of functional crosstalk between biological processes, suggesting general design principles of genetic interactomes. 相似文献
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The use of the budding yeast Saccharomyces cerevisiae as a simple eukaryotic model system for the study of chromatin assembly and regulation has allowed rapid discovery of genes that influence this complex process. The functions of many of the proteins encoded by these genes have not yet been fully characterized. Here, we describe a high-throughput methodology that can be used to illuminate gene function and discuss its application to a set of genes involved in the creation, maintenance and remodeling of chromatin structure. Our technique, termed E-MAPs, involves the generation of quantitative genetic interaction maps that reveal the function and organization of cellular proteins and networks. 相似文献
54.
Nucleotide polymorphism in the acidic chitinase locus (ChiA) region of the wild plant Arabidopsis thaliana 总被引:3,自引:0,他引:3
To investigate DNA variation in natural plant populations, a 1.8-kb region
of the acidic chitinase locus (ChiA)was analyzed for 17 ecotypes of
Arabidopsis thaliana sampled worldwide and 3 Arabis species in Japan. As in
the Adh region, dimorphism was detected throughout the investigated ChiA
region, suggesting the possibility that dimorphic DNA variation exists in
the entire nuclear genome of A. thaliana. The ChiA region was divided into
two blocks by an intragenic recombination between two parental sequence
types, which diverged 7.4 MYA under the assumption that nucleotide mutation
rate per site per year is mu = 10(- 9). Nucleotide diversity in the entire
ChiA region was 0.0104. Tajima's test was significantly negative for both
nucleotide and indel variations, which was manifested as an excess of
unique polymorphisms. However, the level and pattern of polymorphism in the
ChiA region were inconsistent with simple theoretical explanations. The HKA
test detected no difference in the levels of intra- and interspecific
variations between the ChiA and Adh regions. In the ChiA coding region, no
difference in the patterns of synonymous and replacement variation was
found in intra- and interspecific comparisons by the MK test. Although it
was difficult to determine the exact genetic mechanism acting on the ChA
locus, these results suggested that the ChA locus region was under the same
genetic mechanism before and after the establishment of A. thaliana as a
species.
相似文献
55.
Ensemble non-negative matrix factorization methods for clustering protein-protein interactions 总被引:1,自引:0,他引:1
MOTIVATION: When working with large-scale protein interaction data, an important analysis task is the assignment of pairs of proteins to groups that correspond to higher order assemblies. Previously a common approach to this problem has been to apply standard hierarchical clustering methods to identify such a groups. Here we propose a new algorithm for aggregating a diverse collection of matrix factorizations to produce a more informative clustering, which takes the form of a 'soft' hierarchy of clusters. RESULTS: We apply the proposed Ensemble non-negative matrix factorization (NMF) algorithm to a high-quality assembly of binary protein interactions derived from two proteome-wide studies in yeast. Our experimental evaluation demonstrates that the algorithm lends itself to discovering small localized structures in this data, which correspond to known functional groupings of complexes. In addition, we show that the algorithm also supports the assignment of putative functions for previously uncharacterized proteins, for instance the protein YNR024W, which may be an uncharacterized component of the exosome. 相似文献
56.
The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation 总被引:11,自引:0,他引:11
57.
Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II 下载免费PDF全文
58.
Matthew Jessulat Ramy H. Malty Diem-Hang Nguyen-Tran Viktor Deineko Hiroyuki Aoki James Vlasblom Katayoun Omidi Ke Jin Zoran Minic Mohsen Hooshyar Daniel Burnside Bahram Samanfar Sadhna Phanse Tanya Freywald Bhanu Prasad Zhaolei Zhang Franco Vizeacoumar Nevan J. Krogan Andrew Freywald Ashkan Golshani Mohan Babu 《Molecular and cellular biology》2015,35(14):2448-2463
The nonhomologous end-joining (NHEJ) pathway is essential for the preservation of genome integrity, as it efficiently repairs DNA double-strand breaks (DSBs). Previous biochemical and genetic investigations have indicated that, despite the importance of this pathway, the entire complement of genes regulating NHEJ remains unknown. To address this, we employed a plasmid-based NHEJ DNA repair screen in budding yeast (Saccharomyces cerevisiae) using 369 putative nonessential DNA repair-related components as queries. Among the newly identified genes associated with NHEJ deficiency upon disruption are two spindle assembly checkpoint kinases, Bub1 and Bub2. Both observation of resulting phenotypes and chromatin immunoprecipitation demonstrated that Bub1 and -2, either alone or in combination with cell cycle regulators, are recruited near the DSB, where phosphorylated Rad53 or H2A accumulates. Large-scale proteomic analysis of Bub kinases phosphorylated in response to DNA damage identified previously unknown kinase substrates on Tel1 S/T-Q sites. Moreover, Bub1 NHEJ function appears to be conserved in mammalian cells. 53BP1, which influences DSB repair by NHEJ, colocalizes with human BUB1 and is recruited to the break sites. Thus, while Bub is not a core component of NHEJ machinery, our data support its dual role in mitotic exit and promotion of NHEJ repair in yeast and mammals. 相似文献
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Humberto Martin Michael Shales Pablo Fernandez‐Piñar Ping Wei Maria Molina Dorothea Fiedler Kevan M Shokat Pedro Beltrao Wendell Lim Nevan J Krogan 《Molecular systems biology》2015,11(4)
Genetic interaction screens have been applied with great success in several organisms to study gene function and the genetic architecture of the cell. However, most studies have been performed under optimal growth conditions even though many functional interactions are known to occur under specific cellular conditions. In this study, we have performed a large‐scale genetic interaction analysis in Saccharomyces cerevisiae involving approximately 49 × 1,200 double mutants in the presence of five different stress conditions, including osmotic, oxidative and cell wall‐altering stresses. This resulted in the generation of a differential E‐MAP (or dE‐MAP) comprising over 250,000 measurements of conditional interactions. We found an extensive number of conditional genetic interactions that recapitulate known stress‐specific functional associations. Furthermore, we have also uncovered previously unrecognized roles involving the phosphatase regulator Bud14, the histone methylation complex COMPASS and membrane trafficking complexes in modulating the cell wall integrity pathway. Finally, the osmotic stress differential genetic interactions showed enrichment for genes coding for proteins with conditional changes in phosphorylation but not for genes with conditional changes in gene expression. This suggests that conditional genetic interactions are a powerful tool to dissect the functional importance of the different response mechanisms of the cell. 相似文献
60.
Jeffrey R. Johnson Silvia D. Santos Tasha Johnson Ursula Pieper Marta Strumillo Omar Wagih Andrej Sali Nevan J. Krogan Pedro Beltrao 《PLoS computational biology》2015,11(8)
The African clawed frog Xenopus laevis is an important model organism for studies in developmental and cell biology, including cell-signaling. However, our knowledge of X. laevis protein post-translational modifications remains scarce. Here, we used a mass spectrometry-based approach to survey the phosphoproteome of this species, compiling a list of 2636 phosphosites. We used structural information and phosphoproteomic data for 13 other species in order to predict functionally important phospho-regulatory events. We found that the degree of conservation of phosphosites across species is predictive of sites with known molecular function. In addition, we predicted kinase-protein interactions for a set of cell-cycle kinases across all species. The degree of conservation of kinase-protein interactions was found to be predictive of functionally relevant regulatory interactions. Finally, using comparative protein structure models, we find that phosphosites within structured domains tend to be located at positions with high conformational flexibility. Our analysis suggests that a small class of phosphosites occurs in positions that have the potential to regulate protein conformation. 相似文献