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A transcriptional timetable of autumn senescence -: art. no. R24

GENOME BIOLOGY 2004年第4期5卷 1-13页

作者： Andersson, A Keskitalo, J Sjödin, A Bhalerao, R Sterky, F Wissel, K Tandre, K Aspeborg, H Moyle, R Ohmiya, Y Bhalerao, R Brunner, A Gustafsson, P Karlsson, J Lundeberg, J Nilsson, O Sandberg, G Strauss, S Sundberg, B Uhlen, M Jansson, S Nilsson, P Umea Univ Dept Plant Physiol Umea Plant Sci Ctr SE-90187 Umea Sweden AlbaNova Univ Ctr Royal Inst Technol KTH Dept Biotechnol SE-10691 Stockholm Sweden Swedish Univ Agr Sci Dept Forest Genet & Plant Physiol Umea Plant Sci Ctr SE-90183 Umea Sweden Oregon State Univ Dept Forest Sci Corvallis OR 97331 USA

Background: We have developed genomic tools to allow the genus Populus ( aspens and cottonwoods) to be exploited as a full-featured model for investigating fundamental aspects of tree biology. We have undertaken large-scale expressed sequence tag ( EST) sequencing programs and created Populus microarrays with significant gene coverage. One of the important aspects of plant biology that cannot be studied in annual plants is the gene activity involved in the induction of autumn leaf senescence. Results: On the basis of 36,354 Populus ESTs, obtained from seven cDNA libraries, we have created a DNA microarray consisting of 13,490 clones, spotted in duplicate. Of these clones, 12,376 (92%) were confirmed by resequencing and all sequences were annotated and functionally classified. Here we have used the microarray to study transcript abundance in leaves of a free-growing aspen tree ( Populus tremula) in northern Sweden during natural autumn senescence. Of the 13,490 spotted clones, 3,792 represented genes with significant expression in all leaf samples from the seven studied dates. Conclusions: We observed a major shift in gene expression, coinciding with massive chlorophyll degradation, that reflected a shift from photosynthetic competence to energy generation by mitochondrial respiration, oxidation of fatty acids and nutrient mobilization. Autumn senescence had much in common with senescence in annual plants;for example many proteases were induced. We also found evidence for increased transcriptional activity before the appearance of visible signs of senescence, presumably preparing the leaf for degradation of its components.

关键词： Leaf Senescence additional data file Annual Plant Aspen Tree Autumn Leaf

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Exon expression profiling reveals stimulus-mediated exon use in neural cells

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GENOME BIOLOGY 2007年第8期8卷 R159-R159页

作者： Mckee, Adrienne E. Neretti, Nicola Carvalho, Luis E. Meyer, Clifford A. Fox, Edward A. Brodsky, Alexander S. Silver, Pamela A. Brown Univ Dept Mol Biol Cell Biol & Biochem Providence RI 02903 USA Harvard Univ Sch Med Dept Syst Biol Boston MA 02115 USA Brown Univ Dept Phys Inst Brain & Neural Syst Providence RI 02912 USA Brown Univ Ctr Computat Mol Biol Providence RI 02912 USA Brown Univ Dept Appl Math Providence RI 02912 USA Dana Farber Canc Inst Dept Biostat & Computat Biol Boston MA 02115 USA Harvard Univ Sch Publ Hlth Dept Biostat Boston MA 02115 USA Harvard Univ Sch Med Dept Med Boston MA 02115 USA Dana Farber Canc Inst Dept Med Oncol Boston MA 02115 USA Brown Univ Ctr Genom & Proteom Ctr Computat Mol Biol Providence RI 02903 USA

Background: Neuronal cells respond to changes in intracellular calcium ([Ca2+](i)) by affecting both the abundance and architecture of specific mRNAs. Although calcium-induced transcription and transcript variation have both been recognized as important sources of gene regulation, the interplay between these two phenomena has not been evaluated on a genome-wide scale. Results: Here, we show that exon-centric microarrays can be used to resolve the [Ca2+](i)(-) modulated gene expression response into transcript-level and exon-level regulation. Global assessments of affected transcripts reveal modulation within distinct functional gene categories. We find that transcripts containing calcium-modulated exons exhibit enrichment for calcium ion binding, calmodulin binding, plasma membrane associated, and metabolic proteins. additionally, we uncover instances of regulated exon use in potassium channels, neuroendocrine secretory proteins and metabolic enzymes, and demonstrate that regulated changes in exon expression give rise to distinct transcript variants. Conclusion: Our findings connect extracellular stimuli to specific exon behavior, and suggest that changes in transcript and exon abundance are reflective of a coordinated gene expression response to elevated [Ca2+](i). The technology we describe here lends itself readily to the resolution of stimulus-induced gene expression at both the transcript and exon levels.

关键词： Gene Ontology Alternative Splice Endoplasmic Reticulum Stress additional data file Splice Form

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Diversity and evolution of phycobilisomes in marine Synechococcus spp.:: a comparative genomics study

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GENOME BIOLOGY 2007年第12期8卷 R259-R259页

作者： Six, Christophe Thomas, Jean-Claude Garczarek, Laurence Ostrowski, Martin Dufresne, Alexis Blot, Nicolas Scanlan, David J. Partensky, Frederic Univ Paris 06 UMR 7144 F-29682 Roscoff France CNRS Biol Stn Grp Plancton Ocean F-29682 Roscoff France Mt Allison Univ Photosynth Mol Ecophysiol Grp Dept Biol Sackville NB E4L 1G7 Canada CNRS UMR 8186 F-75230 Paris France Ecole Normale Super F-75230 Paris France Univ Warwick Dept Biol Sci Coventry CV4 7AL W Midlands England

Background: Marine Synechococcus owe their specific vivid color (ranging from blue-green to orange) to their large extrinsic antenna complexes called phycobilisomes, comprising a central allophycocyanin core and rods of variable phycobiliprotein composition. Three major pigment types can be defined depending on the major phycobiliprotein found in the rods (phycocyanin, phycoerythrin I or phycoerythrin II). Among strains containing both phycoerythrins I and II, four subtypes can be distinguished based on the ratio of the two chromophores bound to these phycobiliproteins. Genomes of eleven marine Synechococcus strains recently became available with one to four strains per pigment type or subtype, allowing an unprecedented comparative genomics study of genes involved in phycobilisome metabolism. Results: By carefully comparing the Synechococcus genomes, we have retrieved candidate genes potentially required for the synthesis of phycobiliproteins in each pigment type. This includes linker polypeptides, phycobilin lyases and a number of novel genes of uncharacterized function. Interestingly, strains belonging to a given pigment type have similar phycobilisome gene complements and organization, independent of the core genome phylogeny (as assessed using concatenated ribosomal proteins). While phylogenetic trees based on concatenated allophycocyanin protein sequences are congruent with the latter, those based on phycocyanin and phycoerythrin notably differ and match the Synechococcus pigment types. Conclusion: We conclude that the phycobilisome core has likely evolved together with the core genome, while rods must have evolved independently, possibly by lateral transfer of phycobilisome rod genes or gene clusters between Synechococcus strains, either via viruses or by natural transformation, allowing rapid adaptation to a variety of light niches.

关键词： additional data file Lyase Gene Pigment Type Cysteinyl Residue Synechococcus Strain

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Growth-rate regulated genes have profound impact on interpretation of transcriptome profiling in Saccharomyces cerevisiae

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GENOME BIOLOGY 2006年第11期7卷 R107-R107页

作者： Regenberg, Birgitte Grotkjaer, Thomas Winther, Ole Fausboll, Anders Akesson, Mats Bro, Christoffer Hansen, Lars Kai Brunak, Soren Nielsen, Jens Goethe Univ Frankfurt Inst Mol Biowissensch D-60438 Frankfurt Germany Tech Univ Denmark BioCent Ctr Microbial Biotechnol DK-2800 Lyngby Denmark Tech Univ Denmark BioCent Ctr Biol Sequence Anal DK-2800 Lyngby Denmark

Background: Growth rate is central to the development of cells in all organisms. However, little is known about the impact of changing growth rates. We used continuous cultures to control growth rate and studied the transcriptional program of the model eukaryote Saccharomyces cerevisiae, with generation times varying between 2 and 35 hours. Results: A total of 5930 transcripts were identified at the different growth rates studied. Consensus clustering of these revealed that half of all yeast genes are affected by the specific growth rate, and that the changes are similar to those found when cells are exposed to different types of stress (> 80% overlap). Genes with decreased transcript levels in response to faster growth are largely of unknown function (> 50%) whereas genes with increased transcript levels are involved in macromolecular biosynthesis such as those that encode ribosomal proteins. This group also covers most targets of the transcriptional activator RAP1, which is also known to be involved in replication. A positive correlation between the location of replication origins and the location of growth-regulated genes suggests a role for replication in growth rate regulation. Conclusion: Our data show that the cellular growth rate has great influence on transcriptional regulation. This, in turn, implies that one should be cautious when comparing mutants with different growth rates. Our findings also indicate that much of the regulation is coordinated via the chromosomal location of the affected genes, which may be valuable information for the control of heterologous gene expression in metabolic engineering.

关键词： Specific Growth Rate additional data file Replication Origin Consensus Cluster Glyoxylate Shunt

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Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-κB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility

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ARTHRITIS RESEARCH & THERAPY 2009年第2期11卷 1-8页

作者： Dieguez-Gonzalez, Rebeca Calaza, Manuel Perez-Pampin, Eva Balsa, Alejandro Blanco, Francisco J. Canete, Juan D. Caliz, Rafael Carreno, Luis de la Serna, Arturo R. Fernandez-Gutierrez, Benjamin Maria Ortiz, Ana Herrero-Beaumont, Gabriel Pablos, Jose L. Narvaez, Javier Navarro, Federico Marenco, Jose L. Gomez-Reino, Juan J. Gonzalez, Antonio Univ Santiago Hosp Clin Lab Invest 2 Santiago De Compostela 15706 Spain Univ Santiago Hosp Clin Rheumatol Unit Santiago De Compostela 15706 Spain Hosp La Paz Rheumatol Unit Madrid 28046 Spain Hosp Univ Juan Canalejo Serv Reumatol Lab Invest Osteoarticular & Envejecimiento La Coruna 15006 Spain Hosp Clin Barcelona Inst Invest Biomed August Pi Sunyer Arthritis Unit Dept Rheumatol Barcelona 08036 Spain Hosp Univ Virgen de las Nieves Rheumatol Unit Granada 18001 Spain Hosp Univ Gregorio Maranon Rheumatol Unit Madrid 28007 Spain Hop Santa Creu & San Pau Rheumatol Unit Barcelona 08025 Spain Hosp Clin San Carlos Rheumatol Unit Madrid 28040 Spain Hosp Univ Princesa Rheumatol Unit Madrid 28006 Spain Fdn Jimenez Diaz Rheumatol Unit Madrid 28040 Spain Hosp 12 Octubre Rheumatol Unit E-28041 Madrid Spain Hosp Univ Bellvitge Rheumatol Unit Barcelona 08907 Spain Hosp Univ Virgen Macarena Rheumatol Unit Seville 41003 Spain Hosp Univ Valme Rheumatol Unit Seville 41003 Spain Univ Santiago de Compostela Dept Med Santiago De Compostela 15705 Spain

Introduction Genome-wide association studies of rheumatoid arthritis (RA) have identified an association of the disease with a 6q23 region devoid of genes. TNFAIP3, an RA candidate gene, flanks this region, and polymorphisms in both the TNFAIP3 gene and the intergenic region are associated with systemic lupus erythematosus. We hypothesized that there is a similar association with RA, including polymorphisms in TNFAIP3 and the intergenic region. Methods To test this hypothesis, we selected tag-single nucleotide polymorphisms (SNPs) in both loci. They were analyzed in 1,651 patients with RA and 1,619 control individuals of Spanish ancestry. Results Weak evidence of association was found both in the 6q23 intergenic region and in the TNFAIP3 locus. The rs582757 SNP and a common haplotype in the TNFAIP3 locus exhibited association with RA. In the intergenic region, two SNPs were associated, namely rs609438 and rs13207033. The latter was only associated in patients with anti-citrullinated peptide antibodies. Overall, statistical association was best explained by the interdependent contribution of SNPs from the two loci TNFAIP3 and the 6q23 intergenic region. Conclusions Our data are consistent with the hypothesis that several RA genetic factors exist in the 6q23 region, including polymorphisms in the TNFAIP3 gene, like that previously described for systemic lupus erythematosus.

关键词： Rheumatoid Arthritis Systemic Lupus Erythematosus Intergenic Region additional data file Control Individual

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Comparative genomic analysis of the odorant-binding protein family in 12 Drosophila genomes:: purifying selection and birth-and-death evolution

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GENOME BIOLOGY 2007年第11期8卷 R235-R235页

作者： Vieira, Filipe G. Sanchez-Gracia, Alejandro Rozas, Julio Univ Barcelona Fac Biol Dept Genet E-08028 Barcelona Spain CSIC Inst Cajal Dept Neurobiol Mol Celular & Desarrollo E-28002 Madrid Spain

Background: Chemoreception is a widespread mechanism that is involved in critical biologic processes, including individual and social behavior. The insect peripheral olfactory system comprises three major multigene families: the olfactory receptor (Or), the gustatory receptor (Gr), and the odorant-binding protein (OBP) families. Members of the latter family establish the first contact with the odorants, and thus constitute the first step in the chemosensory transduction pathway. Results: Comparative analysis of the OBP family in 12 Drosophila genomes allowed the identification of 595 genes that encode putative functional and nonfunctional members in extant species, with 43 gene gains and 28 gene losses (15 deletions and 13 pseudogenization events). The evolution of this family shows tandem gene duplication events, progressive divergence in DNA and amino acid sequence, and prevalence of pseudogenization events in external branches of the phylogenetic tree. We observed that the OBP arrangement in clusters is maintained across the Drosophila species and that purifying selection governs the evolution of the family;nevertheless, OBP genes differ in their functional constraints levels. Finally, we detect that the OBP repertoire evolves more rapidly in the specialist lineages of the Drosophila melanogaster group (D. sechellia and D. erecta) than in their closest generalists. Conclusion: Overall, the evolution of the OBP multigene family is consistent with the birth-and-death model. We also found that members of this family exhibit different functional constraints, which is indicative of some functional divergence, and that they might be involved in some of the specialization processes that occurred through the diversification of the Drosophila genus.

关键词： additional data file Multigene Family Orthologous Group Gene Gain Much Recent Common Ancestor

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The roles of binding site arrangement and combinatorial targeting in microRNA repression of gene expression

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GENOME BIOLOGY 2007年第8期8卷 R166-R166页

作者： Hon, Lawrence S. Zhang, Zemin Genentech Inc Dept Bioinformat San Francisco CA 94080 USA

Background: MicroRNAs (miRNAs) are small noncoding RNAs that bind mRNA target transcripts and repress gene expression. They have been implicated in multiple diseases, such as cancer, but the mechanisms of this involvement are not well understood. Given the complexity and degree of interactions between miRNAs and target genes, understanding how miRNAs achieve their specificity is important to understanding miRNA function and identifying their role in disease. Results: Here we report factors that influence miRNA regulation by considering the effects of both single and multiple miRNAs targeting human genes. In the case of single miRNA targeting, we developed a metric that integrates miRNA and mRNA expression data to calculate how changes in miRNA expression affect target mRNA expression. Using the metric, our global analysis shows that the repression of a given miRNA on a target mRNA is modulated by 3' untranslated region length, the number of target sites, and the distance between a pair of binding sites. additionally, we show that some miRNAs preferentially repress transcripts with longer CTG repeats, suggesting a possible role for miRNAs in repeat expansion disorders such as myotonic dystrophy. We also examine the large class of genes targeted by multiple miRNAs and show that specific types of genes are progressively more enriched as the number of targeting miRNAs increases. Expression microarray data further show that these highly targeted genes are downregulated relative to genes targeted by few miRNAs, which suggests that highly targeted genes are tightly regulated and that their dysregulation may lead to disease. In support of this idea, cancer genes are strongly enriched among highly targeted genes. Conclusion: Our data show that the rules governing miRNA targeting are complex, but that understanding the mechanisms that drive such control can uncover miRNAs' role in disease. Our study suggests that the number and arrangement of miRNA recognition sites can influ

关键词： miRNA Expression additional data file miRNA Target mRNA Expression data miRNA Target Prediction

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Molecular processes during fat cell development revealed by gene expression profiling and functional annotation

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GENOME BIOLOGY 2005年第13期6卷 R108-R108页

作者： Hackl, Hubert Burkard, Thomas Rainer Sturn, Alexander Rubio, Renee Schleiffer, Alexander Tian, Sun Quackenbush, John Eisenhaber, Frank Trajanoski, Zlatko Graz Univ Technol Inst Genom & Bioinformat A-8010 Graz Austria Graz Univ Technol Christian Doppler Lab Genom & Bioinformat A-8010 Graz Austria Res Inst Mol Pathol A-1030 Vienna Austria Dana Farber Canc Inst Dept Biostat & Computat Biol Boston MA 02115 USA

Background: Large-scale transcription profiling of cell models and model organisms can identify novel molecular components involved in fat cell development. Detailed characterization of the sequences of identified gene products has not been done and global mechanisms have not been investigated. We evaluated the extent to which molecular processes can be revealed by expression profiling and functional annotation of genes that are differentially expressed during fat cell development. Results: Mouse microarrays with more than 27,000 elements were developed, and transcriptional profiles of 3T3-L1 cells (pre-adipocyte cells) were monitored during differentiation. In total, 780 differentially expressed expressed sequence tags ( ESTs) were subjected to in-depth bioinformatics analyses. The analysis of 3'-untranslated region sequences from 395 ESTs showed that 71% of the differentially expressed genes could be regulated by microRNAs. A molecular atlas of fat cell development was then constructed by de novo functional annotation on a sequence segment/ domain-wise basis of 659 protein sequences, and subsequent mapping onto known pathways, possible cellular roles, and subcellular localizations. Key enzymes in 27 out of 36 investigated metabolic pathways were regulated at the transcriptional level, typically at the rate-limiting steps in these pathways. Also, coexpressed genes rarely shared consensus transcription-factor binding sites, and were typically not clustered in adjacent chromosomal regions, but were instead widely dispersed throughout the genome. Conclusions: Large-scale transcription profiling in conjunction with sophisticated bioinformatics analyses can provide not only a list of novel players in a particular setting but also a global view on biological processes and molecular networks.

关键词： Metabolic Network additional data file miRNA Target Adipocyte Differentiation Extracellular Matrix Remodel

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Identification of motifs that function in the splicing of non-canonical introns

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GENOME BIOLOGY 2008年第6期9卷 R97-R97页

作者： Murray, Jill I. Voelker, Rodger B. Henscheid, Kristy L. BryanWarf, M. Berglund, J. Andrew Univ Oregon Inst Mol Biol Eugene OR 97403 USA Univ Oregon Dept Chem Eugene OR 97403 USA

Background: While the current model of pre-mRNA splicing is based on the recognition of four canonical intronic motifs (5' splice site, branchpoint sequence, polypyrimidine (PY) tract and 3' splice site), it is becoming increasingly clear that splicing is regulated by both canonical and non-canonical splicing signals located in the RNA sequence of introns and exons that act to recruit the spliceosome and associated splicing factors. The diversity of human intronic sequences suggests the existence of novel recognition pathways for non-canonical introns. This study addresses the recognition and splicing of human introns that lack a canonical PY tract. The PY tract is a uridine-rich region at the 3' end of introns that acts as a binding site for U2AF65, a key factor in splicing machinery recruitment. Results: Human introns were classified computationally into low- and high-scoring PY tracts by scoring the likely U2AF65 binding site strength. Biochemical studies confirmed that low- scoring PY tracts are weak U2AF65 binding sites while high-scoring PY tracts are strong U2AF65 binding sites. A large population of human introns contains weak PY tracts. Computational analysis revealed many families of motifs, including C-rich and G-rich motifs, that are enriched upstream of weak PY tracts. In vivo splicing studies show that C-rich and G-rich motifs function as intronic splicing enhancers in a combinatorial manner to compensate for weak PY tracts. Conclusion: The enrichment of specific intronic splicing enhancers upstream of weak PY tracts suggests that a novel mechanism for intron recognition exists, which compensates for a weakened canonical pre-mRNA splicing motif.

关键词： additional data file Branchpoint Sequence Human Intron Intronic Splice Enhancer Intron Recognition

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Closing gaps in the human genome using sequencing by synthesis

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GENOME BIOLOGY 2009年第6期10卷 R60-R60页

作者： Garber, Manuel Zody, Michael C. Arachchi, Harindra M. Berlin, Aaron Gnerre, Sante Green, Lisa M. Lennon, Niall Nusbaum, Chad Broad Inst MIT & Harvard Genome Sequencing & Anal Program Cambridge MA 02142 USA Uppsala Univ Dept Med Biochem & Microbiol SE-75124 Uppsala Sweden

The most recent release of the finished human genome contains 260 euchromatic gaps (excluding chromosome Y). Recent work has helped explain a large number of these unresolved regions as 'structural' in nature. Another class of gaps is likely to be refractory to clone-based approaches, and cannot be approached in ways previously described. We present an approach for closing these gaps using 454 sequencing. As a proof of principle, we closed all three remaining non-structural gaps in chromosome 15.

关键词： additional data file Segmental Duplication Human Genome Project Celera Assembly Large Insert Clone

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